Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially availa...Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially available vaccine.Live vaccines containing Bb that are widely used abroad are generally efective but can establish latency and potentially reactivate to cause illness in some immunodefcient vaccinated recipients,raising safety concerns.In this study,34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023.The PCR results showed that the percentage of positive Bb was 22.94%(441/1922),and more than 90%of the Bb isolates had four virulence factor-encoding genes(VFGs),namely,fhaB,prn,betA and dnt.All the isolated strains displayed a multidrug-resistant phenotype.The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice,and we found that eight isolates were highly virulent.Furthermore,the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice,and three Bb strains(WH1218,WH1203 and WH1224)with the best protective efcacy were selected.Dogs immunized with these three strains exhibited strong protection against challenge with the Bb feld strain WH1218.Ultimately,the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate.Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb feld strain WH1218.This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China,and all the isolates exhibited multidrug resistance.The present work contributes to the current understanding of the prevalence,antimicrobial resistance,and virulence genes of Bb in domestic dogs and cats.Additionally,our results suggest that the WH1218 strain is a promising candidate 展开更多
Rabies are still a major public health risk in low-and middle-income nations,endangering both human and animal health.Rabies is caused by rabies virus(RABV)from the Rhabdoviridae family of the genus Lyssavirus.The inf...Rabies are still a major public health risk in low-and middle-income nations,endangering both human and animal health.Rabies is caused by rabies virus(RABV)from the Rhabdoviridae family of the genus Lyssavirus.The infection affects the central nervous system,mainly the brain and spinal cord,causing acute encephalitis,which has the highest case fatality rate ever recordednearly 100%.Although all mammals can be infected by RABV,dogs are thought to be the main source of infection.Dog bites cause 95%of human cases of rabies,but in endemic areas,this number increases to 99%(Harischandra,Gunesekera et al.2016).展开更多
Nanoparticles are significant for veterinary vaccine development because they are safer and more effective than conventional formulations.One promising area of research involves self-assembled protein nanoparticles(SA...Nanoparticles are significant for veterinary vaccine development because they are safer and more effective than conventional formulations.One promising area of research involves self-assembled protein nanoparticles(SAPNs),which have shown potential for enhancing antigen-presenting cell uptake,B-cell activation,and lymph node trafficking.Numerous nanovaccines have been utilized in veterinary medicine,including natural self-assembled protein nanoparticles,rationally designed self-assembled protein nanoparticles,animal virus-derived nanoparticles,bacteriophagederived nanoparticles,and plant-derived nanoparticles,which will be discussed in this review.SAPN vaccines can produce robust cellular and humoral immune responses and have been shown to protect against various animal infectious diseases.This article attempts to summarize these diverse nanovaccine types and their recent research progress in the field of veterinary medicine.Furthermore,this paper highlights their disadvantages and methods for improving their immunogenicity.展开更多
Porcine reproductive and respiratory syndrome virus(PRRSV)infection causes significant economic loss to the global pig industry.Genotype 1 and 2 PRRSV(PRRSV-1 and-2)infections have been reported in China,Europe and Am...Porcine reproductive and respiratory syndrome virus(PRRSV)infection causes significant economic loss to the global pig industry.Genotype 1 and 2 PRRSV(PRRSV-1 and-2)infections have been reported in China,Europe and America.For accurate prevention,nanobodies were first used as diagnostic reagents for PRRSV typing.In this study three nanobodies targeting both PRRSV-1 and-2,two targeting PRRSV-1 and three targeting PRRSV-2,were screened and produced.To develop two competitive ELISAs(cELISAs),the g1-2-PRRSV-Nb3-HRP nanobody was chosen for the g1-2-cELISA,to detect common antibodies against PRRSV-1 and-2,and the g1-PRRSV-Nb136-HRP nanobody was chosen for the g1-cELISA,to detect anti-PRRSV-1 antibodies.The two cELISAs were developed using PRRSV-1-N protein as coating antigen,and the amounts for both were 100 ng/well.The optimized dilution of testing pig sera was 1:20,the optimized reaction times were 30 min,and the colorimetric reaction times were 15 min.Then,the cut-off values of the g1-2-cELISA and g1-cELISA were 26.6%and 35.6%,respectively.Both of them have high sensitivity,strong specificity,good repeatability,and stability.In addition,for the 1534 clinical pig sera,an agreement rate of 99.02%(Kappa values=0.97)was determined between the g1-2-cELISA and the commercial IDEXX ELISA kit.For the g1-cELSIA,it can specifically detect anti-PRRSV-1 antibodies in the clinical pig sera.Importantly,combining two nanobody-based cELISAs can differentially detect antibodies against PRRSV-1 and-2.展开更多
Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vac...Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vaccination.Here,we used the chronic social defeat stress(CSDS)model to explore the effects of depression on BCG vaccination efficacy.We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice.Meanwhile,a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay(MGIA).Cytokine expression of IL-12p40,IL-1β,IL-17,TNF-αand IFN-γwas reduced,whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice.Moreover,the proportions of CD4^(+)IFN-γ^(+),CD8^(+)IFN-γ^(+)T lymphocytes and CD4^(+)effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice.Depression promotes CD4^(+)regulatory T cells(Treg)and myeloid-derived suppressor cell(MDSC)generation in depressed mice,contributing to the reduced pro-inflammatory immune response upon BCG vaccination.This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.展开更多
This is the first report on the screening,expression,and recognition mechanism analysis of single-chain fragment variable(scFv)against phenylethanolamine A(PEAA),a newly emergedβ-adrenergic agonist illegally used as ...This is the first report on the screening,expression,and recognition mechanism analysis of single-chain fragment variable(scFv)against phenylethanolamine A(PEAA),a newly emergedβ-adrenergic agonist illegally used as a feed additive for growth promotion.The PEAA-specific scFv scFv,called scFv-32,was screened from hybridoma cell lines by phage display and was found to be optimally expressed in the E.coli system.The ic-ELISA results revealed an IC_(50)value of 10.34μg/L for scFv-32 and no cross-reactivity with otherβ-adrenergic agonists.Homology modeling and molecular docking revealed the key binding sites VAL178,TYP228,and ASP229.One hydrogen bond,two pisigma bonds,and one pi-pi bond maintain the formation of the antibody‒drug complex.Alanine scanning mutagenesis of the three predicted key binding sites showed that the mutants completely lost their recognition activity,which confirmed the accuracy of the theoretical analysis.These results are valuable for the preparation of scFvs and the analysis of the molecular recognition mechanism of antigen-antibodies.展开更多
Bovine coronavirus(BCoV)poses a significant threat to the global cattle industry,causing both respiratory and gastrointestinal infections in cattle populations.This necessitates the development of efficacious vaccines...Bovine coronavirus(BCoV)poses a significant threat to the global cattle industry,causing both respiratory and gastrointestinal infections in cattle populations.This necessitates the development of efficacious vaccines.While several inactivated and live BCoV vaccines exist,they are predominantly limited to calves.The immunization of adult cattle is imperative for BCoV infection control,as it curtails viral transmission to calves and ameliorates the impact of enteric and respiratory ailments across all age groups within the herd.This study presents an in silico methodology for devising a multiepitope vaccine targeting BCoV.The spike glycoprotein(S)and nucleocapsid(N)proteins,which are integral elements of the BCoV structure,play pivotal roles in the viral infection cycle and immune response.We constructed a remarkably effective multiepitope vaccine candidate specifically designed to combat the BCoV population.Using immunoinformatics technology,B-cell and T-cell epitopes were predicted and linked together using linkers and adjuvants to efficiently trigger both cellular and humoral immune responses in cattle.The in silico construct was characterized,and assessment of its physicochemical properties revealed the formation of a stable vaccine construct.After 3D modeling of the vaccine construct,molecular docking revealed a stable interaction with the bovine receptor bTLR4.Moreover,the viability of the vaccine’s high expression and simple purification was demonstrated by codon optimization and in silico cloning expression into the pET28a(+)vector.By applying immunoinformatics approaches,researchers aim to better understand the immune response to bovine coronavirus,discover potential targets for intervention,and facilitate the development of diagnostic tools and vaccines to mitigate the impact of this virus on cattle health and the livestock industry.We anticipate that the design will be useful as a preventive treatment for BCoV sickness in cattle,opening the door for further laboratory studies.展开更多
Sheep pox, goat pox, and lumpy skin diseases are economically significant and contagious viral diseases of sheep, goats and cattle, respectively, caused by the genus Capripoxvirus (CaPV) of the family Poxviridae. Curr...Sheep pox, goat pox, and lumpy skin diseases are economically significant and contagious viral diseases of sheep, goats and cattle, respectively, caused by the genus Capripoxvirus (CaPV) of the family Poxviridae. Currently, CaPV infection of small ruminants (sheep and goats) has been distributed widely and are prevalent in Central Africa, the Middle East, Europe and Asia. This disease poses challenges to food production and distribution, affecting rural livelihoods in most African countries, including Ethiopia. Transmission occurs mainly by direct or indirect contact with infected animals. They cause high morbidity (75-100% in endemic areas) and mortality (10-85%). Additionally, the mortality rate can approach 100% in susceptible animals. Diagnosis largely relies on clinical symptoms, confirmed by laboratory testing using real-time PCR, electron microscopy, virus isolation, serology and histology. Control and eradication of sheep pox virus (SPPV), goat pox virus (GTPV), and lumpy skin disease (LSDV) depend on timely recognition of disease eruption, vector control, and movement restriction. To date, attenuated vaccines originating from KSGPV O-180 strains are effective and widely used in Ethiopia to control CaPV throughout the country. This vaccine strain is clinically safe to control CaPV in small ruminants but not in cattle which may be associated with insufficient vaccination coverage and the production of low-quality vaccines.展开更多
Zoonotic hookworm infections remain a significant public health problem,causing nearly 500 milion cases globally and approximately four million disability-adjusted life years lost annually.More than one-fth of these c...Zoonotic hookworm infections remain a significant public health problem,causing nearly 500 milion cases globally and approximately four million disability-adjusted life years lost annually.More than one-fth of these cases are attrib-uted to Ancylostoma ceylanicum,an emerging zoonotic health issue in the Asia-Pacific region.This review presents key research gaps regarding the epidemiology,diagnosis,control,prevention and elimination of A.ceylanicum and other canine zoonotic hookworms as neglected health threats.A.ceylanicum is the second most prevalent human hook-worm in the region;it is the most common hookworm among dogs and cats-reservoirs of zoonotic infections.Previous population genetic and phylogenetic analyses revealed that A.ceylanicum has three possible transmis-sion dynamics:zoonotic,animal-only,and human-only pathways.The actual burden of zoonotic ancylostomiasis in most endemic countries remains unknown due to the use of parasitological techniques(e.g.,Kato-Katz thick smear and floatation techniques)that have reduced diagnostic performance and do not allow accurate species identifica-tion in helminth surveys.The emergence of benzimidazole resistance in soil-transmitted helminths(STHs),includ-ing hookworms,is a concern due to the protracted implementation of mass drug administration(MDA).Resistance is conferred by single nucleotide polymorphisms(SNPs)that occur in theβ-tubulin isotype 1 gene.These mutations have been reported in drug-resistant A.caninum but have not been found in A.ceylanicum in the field.A.ceylanicum remains understudied in the Asia-Pacific region.The zoonotic nature of the parasite warrants investigation of its occur-rence in human and animal reservoir hosts to understand the dynamics of zoonotic transmission in different endemic foci.The detection of benzimidazole resistance-associated SNPs in zoonotic hookworms from Asia-Pacific countries has yet to be thoroughly explored.Considering the high level of hookworm endemicity in the region,the circulation of resistant isolates between 展开更多
African swine fever(ASF)is a highly contagious disease of domestic and wild pigs caused by African swine fever virus(ASFV).The mortality rate associated with ASF is remarkably high,almost approaching 100%.Since the in...African swine fever(ASF)is a highly contagious disease of domestic and wild pigs caused by African swine fever virus(ASFV).The mortality rate associated with ASF is remarkably high,almost approaching 100%.Since the introduction of ASF into China in 2018,its rapid spread has caused marked economic losses in the country’s swine industry.To date,there are no safe and efective commercial vaccines or antiviral drugs against ASF;thus,there is an urgent need to develop novel prevention and control strategies.Traditional Chinese medicine(TCM),which comprises various herbs that are abundant in various potential functional components,holds great promise for the prevention and control of ASF.Here,we provide a comprehensive review of the advancements in TCM and the efects of its compound formulas against ASF,including the antiviral abilities,immunoregulatory activities,and practical application of these formulas for the prevention and control of ASF.We specifcally examined the potential and constraints of natural product-derived extracts and TCM formulas in combating ASFV.This review aims to ofer insights and ideas for the holistic management and containment of ASF.展开更多
African swine fever(ASF),caused by the ASF virus(ASFV),is an acute,severe,and highly contagious infectious disease in domestic pigs and wild boars.Domestic pigs infected with a virulent ASFV strain can have morbidity ...African swine fever(ASF),caused by the ASF virus(ASFV),is an acute,severe,and highly contagious infectious disease in domestic pigs and wild boars.Domestic pigs infected with a virulent ASFV strain can have morbidity and mortality rates of up to 100%.The epidemic of ASF has caused serious economic losses to the global pig industry.Currently,there is no safe and efective vaccine or specifc drug for treating ASF.Therefore,ASFV still poses a great threat to pig factories.ASFV is a double-stranded DNA virus with a complex icosahedral multilayer structure.The ASFV genome contains 150-170 open reading frames(ORFs)that encode 150-200 proteins.Some ASFV-encoded proteins are involved in virus invasion,genome replication,DNA repair,and virion formation.Some ASFV proteins execute immunomodulatory functions by regulating the host antiviral innate immune response.Accumulating studies have shown that the immunomodulatory functions of ASFV genes are closely related to the virulence and pathogenicity of ASFV isolates.This review summarizes the research advances on ASFV immune evasion mechanisms in African swine fever patients and provides new insights for developing attenuated live vaccine candidates to prevent and control ASF.展开更多
African swine fever(ASF)is an acute and fatal hemorrhagic disease in domestic pigs and wild boars caused by African swine fever virus(ASFV)that currently threatens the pig industry worldwide.Since the 2018 ASF outbrea...African swine fever(ASF)is an acute and fatal hemorrhagic disease in domestic pigs and wild boars caused by African swine fever virus(ASFV)that currently threatens the pig industry worldwide.Since the 2018 ASF outbreak in China,ASFV has evolved and caused diverse clinical manifestations,such as chronic and asymptomatic infections.Therefore,it is important to understand the molecular mechanisms underlying ASFV attenuation in the feld.Here,we isolated three ASFVs from one diseased and two asymptomatic pigs by using primary porcine alveolar macrophages(PAMs)from both domestic pigs and Bama minipigs.The three ASFVs exhibited similar phenotypes in cell culture,includ‑ing cytopathic efects(CPEs),hemadsorptions(HADs),viral protein expressions and growth curves.Genome sequenc‑ing revealed that all three ASFVs were genotype II strains.Genomic comparisons suggested that the disruption of the viral genes MGF360 and MGF110,rather than EP402R and EP153R,is likely involved in the potential attenuation of ASFV via the upregulation of innate immune responses.展开更多
Pathogenic African swine fever virus(ASFV)remains a lethal causative agent in the domestic pig industry,which poses a burden on the swine market and causes substantial socioeconomic losses worldwide.Currently,there ar...Pathogenic African swine fever virus(ASFV)remains a lethal causative agent in the domestic pig industry,which poses a burden on the swine market and causes substantial socioeconomic losses worldwide.Currently,there are no commercially efcacious vaccines or specifc treatments available for ASF prevention and control.Unfortunately,little is known about the swine immune response upon ASFV infection.Here,we investigated the host immune response discrepancy induced by the feld moderately virulent strain ASFV HB-2208 among healthy,diseased and asymptomatic pigs.In the peripheral blood of diseased swine,lymphopenia is caused by the massive loss of bystander lymphocytes,such asγδT cells,B cells and CD4^(+)T cells.Conversely,ASFV has a strong tropism for the mononuclear phagocyte system(MPS)and partial dendritic cells(DCs),whose antigen-presenting ability is impeded by the downregulation of CD80 and MHC I.However,no signifcant diference in the number of CD8α^(high) T cells was detected,whereas the frequencies of NK cells,NKT cells,and regulatory T cells(Tregs)were signifcantly increased.Additionally,an in vitro model was established with a coculture of primary pulmonary alveolar macrophages(PAMs)and peripheral blood mononuclear cells(PBMCs),which signifcantly reducedγδT cells,B cells and CD4^(+)T cells and increased Tregs.The diferentiated immune response might aid in enhancing the understanding of ASFV pathogenesis in suids and provide insights into the mechanism of ASFV-induced lymphopenia for further studies.展开更多
African swine fever(ASF)is a highly fatal hemorrhagic disease afecting domestic pigs caused by African swine fever virus(ASFV).Genetic analysis of ASFV isolates to date has identifed 24 geographically related genotype...African swine fever(ASF)is a highly fatal hemorrhagic disease afecting domestic pigs caused by African swine fever virus(ASFV).Genetic analysis of ASFV isolates to date has identifed 24 geographically related genotypes with various subgroups,but only genotype I and II ASFVs have been reported outside Africa.ASFV genotype II and genotype I viruses were reported in China in 2018 and 2021,respectively.In this study,unique and highly conserved noncoding regions were found between MGF_505-9R and MGF_505-10R in the 188 genomes of ASFV genotypes I and II.A pair of primers was designed on the basis of this region.By optimizing the reaction system and conditions,a SYBR Green I fuorescence PCR assay that can distinguish between ASFV genotypes I and II was established,and the sensitivity,reproducibility and specifcity were evaluated.The detection limit was 1 TCID_(50)/0.1 mL for both genotypes,with no cross-reactivity observed with other common pig pathogens.The intra-and interbatch variation coefcients were both less than 1.2%.Clinical sample detection analysis revealed 47 positive cases out of 100,including 3 for genotype I and 44 for genotype II,aligning with results from the WOAH-recommended and national standard methods.The method developed in this study allows for the diferentiation of ASFV genotypes I and II without the need for genome sequencing,ofering a convenient and rapid approach for ASFV detection and genotype identifcation.展开更多
Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prio...Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion protein.These diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of cervids.Although they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic potential.While the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in Scandinavia.Most importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to humans.The underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion proteins.With the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.展开更多
Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health concern.Globally,prevention and control of emerging and re-emerging animal coronaviruses is a great challenge.The m...Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health concern.Globally,prevention and control of emerging and re-emerging animal coronaviruses is a great challenge.The mecha-nisms of virus-mediated immune responses have important implications for research on virus prevention and control.The antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lympho-cytes,playing an important role in antiviral immune responses.Thus,it can shed light on the development of diagnos-tic methods and novel vaccines.Here,we have reviewed advances in animal coronavirus antigenic epitope research,aiming to provide a reference for the prevention and control of animal and human coronaviruses.展开更多
The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1...The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.展开更多
Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions....Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions.While tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral infections.Despite sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological conditions.In this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.展开更多
Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as&...Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").Despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.展开更多
In the global progress of bone tumor research,established stable and long-lasting transgenic chondrosarcoma(CSA)cell lines are rare,mainly of murine and human origin,while the establishment of canine CSA cell lines ha...In the global progress of bone tumor research,established stable and long-lasting transgenic chondrosarcoma(CSA)cell lines are rare,mainly of murine and human origin,while the establishment of canine CSA cell lines has yet to be reported.This study established a canine CSA cell line to facilitate the basic clinical study of canine CSA.Fifty fve cases of canine osteolytic disease were collected,and more than 10 bone tumor samples from dogs with typical clinical signs were used for primary cell culture.A cell line with stable passaging for more than 100 generations and mouse tumorigenic ability was successfully cultured.According to the clinical characteristics of the dog and the histopathological results of the primary tumor,CSA was diagnosed,and the CSA cell line was designated Mango.Immunohistochemical(IHC)results showed that the immunoreactivity of bone gamma-carboxyglutamate protein(BGLAP),secreted protein acidic and rich in cysteine(SPARC),alkaline phosphatase(ALPL),vimentin(VIM)and S100 were positive.However,the immunoreactivity of pan-cytokeratin(PCK),chromogranin A(CGA),and platelet endothelial cell adhesion molecule-1(CD31)was negative.Immunofuorescence(IF)results showed that the protein expressions in the Mango cell line were consistent with the IHC identifcation of the primary tumor.The Mango cell line’s doubling time was 43.92 h,and the cell formation rate exceeded 20%.There were abnormal chromosome numbers,hetero staining with toluidine blue,and certain calcifcation abilities.It could be passaged stably and continuously without changing the cell morphology and characteristics.In vivo,the cells were successfully injected into the nude mice model with a tumorigenic rate of 100%.The immunophenotype of the xenograft tumor was consistent with that of the primary tumor.Therefore,we efectively established a canine CSA cell line.As a promising cell material,this cell line can be used to construct a tumor-bearing model conducive to the subsequent basic research of canine CSA.Moreover,because of its similarit展开更多
基金the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030007).
文摘Bordetella bronchiseptica(Bb)is recognized as a leading cause of respiratory diseases in dogs and cats.However,epidemiological data on Bb in dogs and cats in China are still limited,and there is no commercially available vaccine.Live vaccines containing Bb that are widely used abroad are generally efective but can establish latency and potentially reactivate to cause illness in some immunodefcient vaccinated recipients,raising safety concerns.In this study,34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023.The PCR results showed that the percentage of positive Bb was 22.94%(441/1922),and more than 90%of the Bb isolates had four virulence factor-encoding genes(VFGs),namely,fhaB,prn,betA and dnt.All the isolated strains displayed a multidrug-resistant phenotype.The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice,and we found that eight isolates were highly virulent.Furthermore,the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice,and three Bb strains(WH1218,WH1203 and WH1224)with the best protective efcacy were selected.Dogs immunized with these three strains exhibited strong protection against challenge with the Bb feld strain WH1218.Ultimately,the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate.Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb feld strain WH1218.This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China,and all the isolates exhibited multidrug resistance.The present work contributes to the current understanding of the prevalence,antimicrobial resistance,and virulence genes of Bb in domestic dogs and cats.Additionally,our results suggest that the WH1218 strain is a promising candidate
文摘Rabies are still a major public health risk in low-and middle-income nations,endangering both human and animal health.Rabies is caused by rabies virus(RABV)from the Rhabdoviridae family of the genus Lyssavirus.The infection affects the central nervous system,mainly the brain and spinal cord,causing acute encephalitis,which has the highest case fatality rate ever recordednearly 100%.Although all mammals can be infected by RABV,dogs are thought to be the main source of infection.Dog bites cause 95%of human cases of rabies,but in endemic areas,this number increases to 99%(Harischandra,Gunesekera et al.2016).
文摘Nanoparticles are significant for veterinary vaccine development because they are safer and more effective than conventional formulations.One promising area of research involves self-assembled protein nanoparticles(SAPNs),which have shown potential for enhancing antigen-presenting cell uptake,B-cell activation,and lymph node trafficking.Numerous nanovaccines have been utilized in veterinary medicine,including natural self-assembled protein nanoparticles,rationally designed self-assembled protein nanoparticles,animal virus-derived nanoparticles,bacteriophagederived nanoparticles,and plant-derived nanoparticles,which will be discussed in this review.SAPN vaccines can produce robust cellular and humoral immune responses and have been shown to protect against various animal infectious diseases.This article attempts to summarize these diverse nanovaccine types and their recent research progress in the field of veterinary medicine.Furthermore,this paper highlights their disadvantages and methods for improving their immunogenicity.
基金funded by grants from the National Key R&D Program of China(2023YFD1800304)the National Natural Science Foundation of China to QZ(32273041)+1 种基金the Natural Science Foundation of Shaanxi Province of China(2022JC-12)the Central Public-interest Scientific Institution Basal Research Fund,National Data Center of Animal Health.
文摘Porcine reproductive and respiratory syndrome virus(PRRSV)infection causes significant economic loss to the global pig industry.Genotype 1 and 2 PRRSV(PRRSV-1 and-2)infections have been reported in China,Europe and America.For accurate prevention,nanobodies were first used as diagnostic reagents for PRRSV typing.In this study three nanobodies targeting both PRRSV-1 and-2,two targeting PRRSV-1 and three targeting PRRSV-2,were screened and produced.To develop two competitive ELISAs(cELISAs),the g1-2-PRRSV-Nb3-HRP nanobody was chosen for the g1-2-cELISA,to detect common antibodies against PRRSV-1 and-2,and the g1-PRRSV-Nb136-HRP nanobody was chosen for the g1-cELISA,to detect anti-PRRSV-1 antibodies.The two cELISAs were developed using PRRSV-1-N protein as coating antigen,and the amounts for both were 100 ng/well.The optimized dilution of testing pig sera was 1:20,the optimized reaction times were 30 min,and the colorimetric reaction times were 15 min.Then,the cut-off values of the g1-2-cELISA and g1-cELISA were 26.6%and 35.6%,respectively.Both of them have high sensitivity,strong specificity,good repeatability,and stability.In addition,for the 1534 clinical pig sera,an agreement rate of 99.02%(Kappa values=0.97)was determined between the g1-2-cELISA and the commercial IDEXX ELISA kit.For the g1-cELSIA,it can specifically detect anti-PRRSV-1 antibodies in the clinical pig sera.Importantly,combining two nanobody-based cELISAs can differentially detect antibodies against PRRSV-1 and-2.
基金funded by the National Natural Science Foundation of China(Grant No.U21A20259,31602061,31872470)the National Key Research and Development Program of China(Grant No.2021YFD1800401).
文摘Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vaccination.Here,we used the chronic social defeat stress(CSDS)model to explore the effects of depression on BCG vaccination efficacy.We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice.Meanwhile,a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay(MGIA).Cytokine expression of IL-12p40,IL-1β,IL-17,TNF-αand IFN-γwas reduced,whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice.Moreover,the proportions of CD4^(+)IFN-γ^(+),CD8^(+)IFN-γ^(+)T lymphocytes and CD4^(+)effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice.Depression promotes CD4^(+)regulatory T cells(Treg)and myeloid-derived suppressor cell(MDSC)generation in depressed mice,contributing to the reduced pro-inflammatory immune response upon BCG vaccination.This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.
基金the National Natural Science Foundation of China(32072920)the Fundamental Research Funds for the Central Universities(2662022DKPY007)the HZAU-AGIS Cooperation Fund(SZYJY2022024).
文摘This is the first report on the screening,expression,and recognition mechanism analysis of single-chain fragment variable(scFv)against phenylethanolamine A(PEAA),a newly emergedβ-adrenergic agonist illegally used as a feed additive for growth promotion.The PEAA-specific scFv scFv,called scFv-32,was screened from hybridoma cell lines by phage display and was found to be optimally expressed in the E.coli system.The ic-ELISA results revealed an IC_(50)value of 10.34μg/L for scFv-32 and no cross-reactivity with otherβ-adrenergic agonists.Homology modeling and molecular docking revealed the key binding sites VAL178,TYP228,and ASP229.One hydrogen bond,two pisigma bonds,and one pi-pi bond maintain the formation of the antibody‒drug complex.Alanine scanning mutagenesis of the three predicted key binding sites showed that the mutants completely lost their recognition activity,which confirmed the accuracy of the theoretical analysis.These results are valuable for the preparation of scFvs and the analysis of the molecular recognition mechanism of antigen-antibodies.
文摘Bovine coronavirus(BCoV)poses a significant threat to the global cattle industry,causing both respiratory and gastrointestinal infections in cattle populations.This necessitates the development of efficacious vaccines.While several inactivated and live BCoV vaccines exist,they are predominantly limited to calves.The immunization of adult cattle is imperative for BCoV infection control,as it curtails viral transmission to calves and ameliorates the impact of enteric and respiratory ailments across all age groups within the herd.This study presents an in silico methodology for devising a multiepitope vaccine targeting BCoV.The spike glycoprotein(S)and nucleocapsid(N)proteins,which are integral elements of the BCoV structure,play pivotal roles in the viral infection cycle and immune response.We constructed a remarkably effective multiepitope vaccine candidate specifically designed to combat the BCoV population.Using immunoinformatics technology,B-cell and T-cell epitopes were predicted and linked together using linkers and adjuvants to efficiently trigger both cellular and humoral immune responses in cattle.The in silico construct was characterized,and assessment of its physicochemical properties revealed the formation of a stable vaccine construct.After 3D modeling of the vaccine construct,molecular docking revealed a stable interaction with the bovine receptor bTLR4.Moreover,the viability of the vaccine’s high expression and simple purification was demonstrated by codon optimization and in silico cloning expression into the pET28a(+)vector.By applying immunoinformatics approaches,researchers aim to better understand the immune response to bovine coronavirus,discover potential targets for intervention,and facilitate the development of diagnostic tools and vaccines to mitigate the impact of this virus on cattle health and the livestock industry.We anticipate that the design will be useful as a preventive treatment for BCoV sickness in cattle,opening the door for further laboratory studies.
文摘Sheep pox, goat pox, and lumpy skin diseases are economically significant and contagious viral diseases of sheep, goats and cattle, respectively, caused by the genus Capripoxvirus (CaPV) of the family Poxviridae. Currently, CaPV infection of small ruminants (sheep and goats) has been distributed widely and are prevalent in Central Africa, the Middle East, Europe and Asia. This disease poses challenges to food production and distribution, affecting rural livelihoods in most African countries, including Ethiopia. Transmission occurs mainly by direct or indirect contact with infected animals. They cause high morbidity (75-100% in endemic areas) and mortality (10-85%). Additionally, the mortality rate can approach 100% in susceptible animals. Diagnosis largely relies on clinical symptoms, confirmed by laboratory testing using real-time PCR, electron microscopy, virus isolation, serology and histology. Control and eradication of sheep pox virus (SPPV), goat pox virus (GTPV), and lumpy skin disease (LSDV) depend on timely recognition of disease eruption, vector control, and movement restriction. To date, attenuated vaccines originating from KSGPV O-180 strains are effective and widely used in Ethiopia to control CaPV throughout the country. This vaccine strain is clinically safe to control CaPV in small ruminants but not in cattle which may be associated with insufficient vaccination coverage and the production of low-quality vaccines.
文摘Zoonotic hookworm infections remain a significant public health problem,causing nearly 500 milion cases globally and approximately four million disability-adjusted life years lost annually.More than one-fth of these cases are attrib-uted to Ancylostoma ceylanicum,an emerging zoonotic health issue in the Asia-Pacific region.This review presents key research gaps regarding the epidemiology,diagnosis,control,prevention and elimination of A.ceylanicum and other canine zoonotic hookworms as neglected health threats.A.ceylanicum is the second most prevalent human hook-worm in the region;it is the most common hookworm among dogs and cats-reservoirs of zoonotic infections.Previous population genetic and phylogenetic analyses revealed that A.ceylanicum has three possible transmis-sion dynamics:zoonotic,animal-only,and human-only pathways.The actual burden of zoonotic ancylostomiasis in most endemic countries remains unknown due to the use of parasitological techniques(e.g.,Kato-Katz thick smear and floatation techniques)that have reduced diagnostic performance and do not allow accurate species identifica-tion in helminth surveys.The emergence of benzimidazole resistance in soil-transmitted helminths(STHs),includ-ing hookworms,is a concern due to the protracted implementation of mass drug administration(MDA).Resistance is conferred by single nucleotide polymorphisms(SNPs)that occur in theβ-tubulin isotype 1 gene.These mutations have been reported in drug-resistant A.caninum but have not been found in A.ceylanicum in the field.A.ceylanicum remains understudied in the Asia-Pacific region.The zoonotic nature of the parasite warrants investigation of its occur-rence in human and animal reservoir hosts to understand the dynamics of zoonotic transmission in different endemic foci.The detection of benzimidazole resistance-associated SNPs in zoonotic hookworms from Asia-Pacific countries has yet to be thoroughly explored.Considering the high level of hookworm endemicity in the region,the circulation of resistant isolates between
基金funded by the Postdoctoral Fellowship Program of CPSF(Grant No.GZB20230245).
文摘African swine fever(ASF)is a highly contagious disease of domestic and wild pigs caused by African swine fever virus(ASFV).The mortality rate associated with ASF is remarkably high,almost approaching 100%.Since the introduction of ASF into China in 2018,its rapid spread has caused marked economic losses in the country’s swine industry.To date,there are no safe and efective commercial vaccines or antiviral drugs against ASF;thus,there is an urgent need to develop novel prevention and control strategies.Traditional Chinese medicine(TCM),which comprises various herbs that are abundant in various potential functional components,holds great promise for the prevention and control of ASF.Here,we provide a comprehensive review of the advancements in TCM and the efects of its compound formulas against ASF,including the antiviral abilities,immunoregulatory activities,and practical application of these formulas for the prevention and control of ASF.We specifcally examined the potential and constraints of natural product-derived extracts and TCM formulas in combating ASFV.This review aims to ofer insights and ideas for the holistic management and containment of ASF.
基金supported by the National Key Research and Development Program of China(Grant No.2021YFD1800100)the National Natural Science Foundation of China(Grant Nos.32172874 and 31941002).
文摘African swine fever(ASF),caused by the ASF virus(ASFV),is an acute,severe,and highly contagious infectious disease in domestic pigs and wild boars.Domestic pigs infected with a virulent ASFV strain can have morbidity and mortality rates of up to 100%.The epidemic of ASF has caused serious economic losses to the global pig industry.Currently,there is no safe and efective vaccine or specifc drug for treating ASF.Therefore,ASFV still poses a great threat to pig factories.ASFV is a double-stranded DNA virus with a complex icosahedral multilayer structure.The ASFV genome contains 150-170 open reading frames(ORFs)that encode 150-200 proteins.Some ASFV-encoded proteins are involved in virus invasion,genome replication,DNA repair,and virion formation.Some ASFV proteins execute immunomodulatory functions by regulating the host antiviral innate immune response.Accumulating studies have shown that the immunomodulatory functions of ASFV genes are closely related to the virulence and pathogenicity of ASFV isolates.This review summarizes the research advances on ASFV immune evasion mechanisms in African swine fever patients and provides new insights for developing attenuated live vaccine candidates to prevent and control ASF.
基金supported by the National Key Research and Develop‑ment Program of China under Grant[2021YFD1800105]the Jiangsu Provincial Key R&D Plan under Grant[BE2020398]+3 种基金the Jiangsu Agricultural Science and Technology Independent Innovation Fund Project under Grant[CX(21)2035]the 111 Project under Grant D18007the A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by Research and Practice Innovation Project of Jiangsu Province Graduate Students(SJCX24_2310).
文摘African swine fever(ASF)is an acute and fatal hemorrhagic disease in domestic pigs and wild boars caused by African swine fever virus(ASFV)that currently threatens the pig industry worldwide.Since the 2018 ASF outbreak in China,ASFV has evolved and caused diverse clinical manifestations,such as chronic and asymptomatic infections.Therefore,it is important to understand the molecular mechanisms underlying ASFV attenuation in the feld.Here,we isolated three ASFVs from one diseased and two asymptomatic pigs by using primary porcine alveolar macrophages(PAMs)from both domestic pigs and Bama minipigs.The three ASFVs exhibited similar phenotypes in cell culture,includ‑ing cytopathic efects(CPEs),hemadsorptions(HADs),viral protein expressions and growth curves.Genome sequenc‑ing revealed that all three ASFVs were genotype II strains.Genomic comparisons suggested that the disruption of the viral genes MGF360 and MGF110,rather than EP402R and EP153R,is likely involved in the potential attenuation of ASFV via the upregulation of innate immune responses.
基金support provided by the National Natural Sciences Foundation of China(Grant Nos.32172873 and 31941005)the National Programme on Key Research Project of China(2021YFD1800105-2)National Natural Sciences Foundation of China,32172873,Min Cui,31941005,Min Cui,National Programme on Key Research Project of China,2021YFD1800105-2,Min Cui。
文摘Pathogenic African swine fever virus(ASFV)remains a lethal causative agent in the domestic pig industry,which poses a burden on the swine market and causes substantial socioeconomic losses worldwide.Currently,there are no commercially efcacious vaccines or specifc treatments available for ASF prevention and control.Unfortunately,little is known about the swine immune response upon ASFV infection.Here,we investigated the host immune response discrepancy induced by the feld moderately virulent strain ASFV HB-2208 among healthy,diseased and asymptomatic pigs.In the peripheral blood of diseased swine,lymphopenia is caused by the massive loss of bystander lymphocytes,such asγδT cells,B cells and CD4^(+)T cells.Conversely,ASFV has a strong tropism for the mononuclear phagocyte system(MPS)and partial dendritic cells(DCs),whose antigen-presenting ability is impeded by the downregulation of CD80 and MHC I.However,no signifcant diference in the number of CD8α^(high) T cells was detected,whereas the frequencies of NK cells,NKT cells,and regulatory T cells(Tregs)were signifcantly increased.Additionally,an in vitro model was established with a coculture of primary pulmonary alveolar macrophages(PAMs)and peripheral blood mononuclear cells(PBMCs),which signifcantly reducedγδT cells,B cells and CD4^(+)T cells and increased Tregs.The diferentiated immune response might aid in enhancing the understanding of ASFV pathogenesis in suids and provide insights into the mechanism of ASFV-induced lymphopenia for further studies.
基金supported by the National Key Research and Development Program of China(Grant No.2023YFF1000901)the Hubei Agricultural Research System(grant number HBHZD-ZB-2020-005)+3 种基金the National Key Research and Development Program of China(grant number 2021YFD1800101-2)Hubei Hongshan Laboratory(No.2022 hszd023)Project 2662023DKPY004supported by the Fundamental Research Funds for the Central Universities.
文摘African swine fever(ASF)is a highly fatal hemorrhagic disease afecting domestic pigs caused by African swine fever virus(ASFV).Genetic analysis of ASFV isolates to date has identifed 24 geographically related genotypes with various subgroups,but only genotype I and II ASFVs have been reported outside Africa.ASFV genotype II and genotype I viruses were reported in China in 2018 and 2021,respectively.In this study,unique and highly conserved noncoding regions were found between MGF_505-9R and MGF_505-10R in the 188 genomes of ASFV genotypes I and II.A pair of primers was designed on the basis of this region.By optimizing the reaction system and conditions,a SYBR Green I fuorescence PCR assay that can distinguish between ASFV genotypes I and II was established,and the sensitivity,reproducibility and specifcity were evaluated.The detection limit was 1 TCID_(50)/0.1 mL for both genotypes,with no cross-reactivity observed with other common pig pathogens.The intra-and interbatch variation coefcients were both less than 1.2%.Clinical sample detection analysis revealed 47 positive cases out of 100,including 3 for genotype I and 44 for genotype II,aligning with results from the WOAH-recommended and national standard methods.The method developed in this study allows for the diferentiation of ASFV genotypes I and II without the need for genome sequencing,ofering a convenient and rapid approach for ASFV detection and genotype identifcation.
基金funded in part by the Center on Emerging and Zoonotic Infectious Diseases(CEZID)of the National Institutes of General Medical Sciences underaward number P20GM130448.
文摘Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion protein.These diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of cervids.Although they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic potential.While the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in Scandinavia.Most importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to humans.The underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion proteins.With the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.
基金supported by the Natural Science Foundation of Zhejiang Province(Q23C180006)the Zhejiang A&F University Talent Initiative Project(118-203402005901).
文摘Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health concern.Globally,prevention and control of emerging and re-emerging animal coronaviruses is a great challenge.The mecha-nisms of virus-mediated immune responses have important implications for research on virus prevention and control.The antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lympho-cytes,playing an important role in antiviral immune responses.Thus,it can shed light on the development of diagnos-tic methods and novel vaccines.Here,we have reviewed advances in animal coronavirus antigenic epitope research,aiming to provide a reference for the prevention and control of animal and human coronaviruses.
基金National Institutes of Health(NIH)(grants R01 A/130092 and Al161085).
文摘The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.
基金supported by US National Institutes of Health grants Al147394,AG069264,Al112844,HL170961 and Al154598 to J.S.
文摘Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions.While tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral infections.Despite sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological conditions.In this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.
文摘Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").Despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.
基金the National Natural Science Foundation of China(Grant Number:32172925).
文摘In the global progress of bone tumor research,established stable and long-lasting transgenic chondrosarcoma(CSA)cell lines are rare,mainly of murine and human origin,while the establishment of canine CSA cell lines has yet to be reported.This study established a canine CSA cell line to facilitate the basic clinical study of canine CSA.Fifty fve cases of canine osteolytic disease were collected,and more than 10 bone tumor samples from dogs with typical clinical signs were used for primary cell culture.A cell line with stable passaging for more than 100 generations and mouse tumorigenic ability was successfully cultured.According to the clinical characteristics of the dog and the histopathological results of the primary tumor,CSA was diagnosed,and the CSA cell line was designated Mango.Immunohistochemical(IHC)results showed that the immunoreactivity of bone gamma-carboxyglutamate protein(BGLAP),secreted protein acidic and rich in cysteine(SPARC),alkaline phosphatase(ALPL),vimentin(VIM)and S100 were positive.However,the immunoreactivity of pan-cytokeratin(PCK),chromogranin A(CGA),and platelet endothelial cell adhesion molecule-1(CD31)was negative.Immunofuorescence(IF)results showed that the protein expressions in the Mango cell line were consistent with the IHC identifcation of the primary tumor.The Mango cell line’s doubling time was 43.92 h,and the cell formation rate exceeded 20%.There were abnormal chromosome numbers,hetero staining with toluidine blue,and certain calcifcation abilities.It could be passaged stably and continuously without changing the cell morphology and characteristics.In vivo,the cells were successfully injected into the nude mice model with a tumorigenic rate of 100%.The immunophenotype of the xenograft tumor was consistent with that of the primary tumor.Therefore,we efectively established a canine CSA cell line.As a promising cell material,this cell line can be used to construct a tumor-bearing model conducive to the subsequent basic research of canine CSA.Moreover,because of its similarit
