Considering that HBV belongs to the DNA virus family and is hepatotropic,we model the HBV DNA-containing capsids as a compartment.In this paper,a delayed HBV infection model is established,where the general incidence ...Considering that HBV belongs to the DNA virus family and is hepatotropic,we model the HBV DNA-containing capsids as a compartment.In this paper,a delayed HBV infection model is established,where the general incidence function and two infection routes including cell-virus infection and cell-cell infection are introduced.According to some preliminaries,including well-posedness,basic reproduction number and existence of two equilibria,we obtain the threshold dynamics for the model.We illustrate numerical simulations to verify the above theoretical results,and furthermore explore the impacts of intracellular delay and cell-cell infection on the global dynamics of the model.展开更多
Foot-and-mouth disease is a highly contagious disease that produces severe economic losses in the livestock industry. This disease is being controlled by the use of an inactivated vaccine. However, the use of recombin...Foot-and-mouth disease is a highly contagious disease that produces severe economic losses in the livestock industry. This disease is being controlled by the use of an inactivated vaccine. However, the use of recombinant empty capsids as a subunit vaccine has been reported to be a promising candidate because it avoids the use of virus in the vaccine production. A plasmid containing the capsid precursor P12A and protease 3C sequences of foot-and-mouth disease virus (FMDV) was constructed and used to compare transient and stable expression in mammalian cells. When BHK-21 cells were transfected with the recombinant vector, protease 3C cleaved the capsid precursor P12A into the structural proteins VP0, VP1 and VP3. A sucrose gradient demonstrated that the structural proteins assembled into different subviral particles. Attempts to generate a stable cell line only allowed isolating low-level-expressing clones, probably due to the effect of protease 3C on the cells. Moreover, the recombinant protein yield achieved in transient expression assays was much higher than the one achieved in stable expression assays. Results indicate that mammalian cells are a good strategy to produce recombinant FMDV subviral particles. However, the alternative approach of transient gene expression in scalable systems should be used instead of the standard method that involves the generation of a stable cell line.展开更多
Grass carp reovirus (GCRV) is a relatively new virus first isolated in China and is a member of the Aquareovirus genus of the Reoviridae family. Recent report of genomic se-quencing showed that GCRV shared high degree...Grass carp reovirus (GCRV) is a relatively new virus first isolated in China and is a member of the Aquareovirus genus of the Reoviridae family. Recent report of genomic se-quencing showed that GCRV shared high degree of homology with mammalian reovirus (MRV). As a step of our effort to understand the structural basis of GCRV pathogenesis, we determined the three-dimensional (3D) structure of GCRV capsid at 17 ? resolution by electron cryomicro-scopy. Each GCRV capsid has a multilayered organization, consisting of an RNA core, an inner, middle and outer protein layer. The outer layer is made up of 200 trimers that are arranged on an incomplete T=13 icosahedral lattice. A characteristic feature of this layer is the depression re-sulting from the absence of trimers around the peripentonal positions, revealing the underlying trimers on the middle layer. There are 120 subunits in the inner layer arranged with T=1 symme-try. These structural features are common to other members of the Reoviridae. Moreover, SDS-PAGE analysis showed that GCRV virions contain seven structural proteins (VP1-VP7). These structural proteins have a high degree of sequence homology to MRV, consistent with the structural similarities observed in our study. The high structural similarities of isolated GCRV and MRV suggest that future structural studies focusing on GCRV entering into and replicating within its host cell are necessary in order to fully understand the structural basis of GCRV pathogenesis.展开更多
The hepatitis B virus （HBV） particle consists of an envelope containing three related surface proteins and probably lipid and an icosahedral nucleocapsid of approximately 30 nm diameter enclosing the viral DNA genom...The hepatitis B virus （HBV） particle consists of an envelope containing three related surface proteins and probably lipid and an icosahedral nucleocapsid of approximately 30 nm diameter enclosing the viral DNA genome and DNA polymerase. The capsid is formed in the cytosol of the infected cell during packaging of an RNA pregenome replication complex by multiple copies of a 21-kDa C protein. The capsid gains the ability to bud during synthesis of the viral DNA genome by reverse transcription of the pregenome in the lumen of the particle. The three envelope proteins S, t4, and L shape a complex transmembrane fold at the endoplasmic reticulum, and form disulfide-linked homoand heterodimers. The transmembrane topology of a fraction of the large envelope protein L changes posttranslationally, therefore, the N terminal domain of L （preS） finally appears on both sides of the membrane. During budding at an intracellular membrane, a short linear domain in the cytosolic preS region interacts with binding sites on the capsid surface. The virions are subsequently secreted into the blood. In addition, the surface proteins can bud in the absence of capsids and form subviral lipoprotein particles of 20 nm diameter which are also secreted.展开更多
Background Non-invasive nasopharyngeal carcinoma （NPC） screening usually involves serological testing for the presence of IgA antibodies to Epstein-Barr virus （EBV） capsid antigen （VCA）. The present meta-analysi...Background Non-invasive nasopharyngeal carcinoma （NPC） screening usually involves serological testing for the presence of IgA antibodies to Epstein-Barr virus （EBV） capsid antigen （VCA）. The present meta-analysis determined the accuracy of VCA-lgA in the diagnosis of NPC.Methods A systematic review of studies was conducted and data on the accuracy of VCA-lgA concentrations in the diagnosis of NPC were pooled using random effects models. Receiver operating characteristic curves were used to summarize the overall test performance. Results Twenty studies met the inclusion criteria for the meta-analysis. The summary estimates for VCA-lgA in the diagnosis of NPC were： sensitivity 0.91 （95% confidence interval （Cl）： 0.90-0.92）, specificity 0.92 （95% Cl： 0.92-0.93）, positive likelihood ratio 31.65 （95% Cl： 10.99-91.15）, negative likelihood ratio 0.10 （95% Cl： 0.07-0.13） and diagnostic odds ratio 414.59 （95% Cl： 174.96-982.42）. The area under the summary receiver operating characteristic curves was 0.98.Conclusion The sensitivity and the specificity of serum VCA-lgA are very high, suggesting that the presence of VCA-lgA in peripheral blood is a valuable predictor for NPC.展开更多
Dear Editor,Astrovirus is an enteric virus associated with sporadic diarrhea or large outbreaks of gastroenteritis（Mendez et al.,2013）.Until 2008,human astroviruses（HAst Vs）were classified into eight serotypes—HA...Dear Editor,Astrovirus is an enteric virus associated with sporadic diarrhea or large outbreaks of gastroenteritis（Mendez et al.,2013）.Until 2008,human astroviruses（HAst Vs）were classified into eight serotypes—HAstV-1 to HAstV-8—based on the reactivity of their capsid protein with type-specific antibodies.Among these serotypes,HAstV-1is the most prevalent globally.However,some divergent new astroviruses（MLB1/MLB2,VA1/VA2/VA3,展开更多
Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines,the epidemic prevention and control are still challenging.Here,we employ a capsid and antige...Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines,the epidemic prevention and control are still challenging.Here,we employ a capsid and antigen structure engineering(CASE)strategy to manufacture an adenoassociated viral serotype 6-based vaccine(S663V-RBD),which expresses trimeric receptor binding domain(RBD)of spike protein fused with a biological adjuvant RS09.Impressively,the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months.Compared to the licensed BBIBP-CorV(Sinopharm,China),a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type,C.37(Lambda)and B.1.617.2(Delta).More interestingly,the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid.Given its effectiveness,the CASE-based S663VRBD may provide a new solution for the current and next pandemic.展开更多
基金Supported by the Natural Science Foundation of Shanxi Province(202303021211003)the National Natural Science Foundation of China(12126349,11601293,12361102)the Scientific Plan of Guizhou Province(No.Qian Ke He Jichu-ZK[2021]YiBan002).
文摘Considering that HBV belongs to the DNA virus family and is hepatotropic,we model the HBV DNA-containing capsids as a compartment.In this paper,a delayed HBV infection model is established,where the general incidence function and two infection routes including cell-virus infection and cell-cell infection are introduced.According to some preliminaries,including well-posedness,basic reproduction number and existence of two equilibria,we obtain the threshold dynamics for the model.We illustrate numerical simulations to verify the above theoretical results,and furthermore explore the impacts of intracellular delay and cell-cell infection on the global dynamics of the model.
文摘Foot-and-mouth disease is a highly contagious disease that produces severe economic losses in the livestock industry. This disease is being controlled by the use of an inactivated vaccine. However, the use of recombinant empty capsids as a subunit vaccine has been reported to be a promising candidate because it avoids the use of virus in the vaccine production. A plasmid containing the capsid precursor P12A and protease 3C sequences of foot-and-mouth disease virus (FMDV) was constructed and used to compare transient and stable expression in mammalian cells. When BHK-21 cells were transfected with the recombinant vector, protease 3C cleaved the capsid precursor P12A into the structural proteins VP0, VP1 and VP3. A sucrose gradient demonstrated that the structural proteins assembled into different subviral particles. Attempts to generate a stable cell line only allowed isolating low-level-expressing clones, probably due to the effect of protease 3C on the cells. Moreover, the recombinant protein yield achieved in transient expression assays was much higher than the one achieved in stable expression assays. Results indicate that mammalian cells are a good strategy to produce recombinant FMDV subviral particles. However, the alternative approach of transient gene expression in scalable systems should be used instead of the standard method that involves the generation of a stable cell line.
基金The research in Dr.Zhou’s lab is supported by NIH(Grant Nos.AI46420&CA94809)the Welch Foundation(AU-1492)+1 种基金 the American Heart Association(Grant No.0240216N)This work was supported by the National Natural Science Foundation of China(Grant Nos.30170730&30470074).
文摘Grass carp reovirus (GCRV) is a relatively new virus first isolated in China and is a member of the Aquareovirus genus of the Reoviridae family. Recent report of genomic se-quencing showed that GCRV shared high degree of homology with mammalian reovirus (MRV). As a step of our effort to understand the structural basis of GCRV pathogenesis, we determined the three-dimensional (3D) structure of GCRV capsid at 17 ? resolution by electron cryomicro-scopy. Each GCRV capsid has a multilayered organization, consisting of an RNA core, an inner, middle and outer protein layer. The outer layer is made up of 200 trimers that are arranged on an incomplete T=13 icosahedral lattice. A characteristic feature of this layer is the depression re-sulting from the absence of trimers around the peripentonal positions, revealing the underlying trimers on the middle layer. There are 120 subunits in the inner layer arranged with T=1 symme-try. These structural features are common to other members of the Reoviridae. Moreover, SDS-PAGE analysis showed that GCRV virions contain seven structural proteins (VP1-VP7). These structural proteins have a high degree of sequence homology to MRV, consistent with the structural similarities observed in our study. The high structural similarities of isolated GCRV and MRV suggest that future structural studies focusing on GCRV entering into and replicating within its host cell are necessary in order to fully understand the structural basis of GCRV pathogenesis.
文摘The hepatitis B virus （HBV） particle consists of an envelope containing three related surface proteins and probably lipid and an icosahedral nucleocapsid of approximately 30 nm diameter enclosing the viral DNA genome and DNA polymerase. The capsid is formed in the cytosol of the infected cell during packaging of an RNA pregenome replication complex by multiple copies of a 21-kDa C protein. The capsid gains the ability to bud during synthesis of the viral DNA genome by reverse transcription of the pregenome in the lumen of the particle. The three envelope proteins S, t4, and L shape a complex transmembrane fold at the endoplasmic reticulum, and form disulfide-linked homoand heterodimers. The transmembrane topology of a fraction of the large envelope protein L changes posttranslationally, therefore, the N terminal domain of L （preS） finally appears on both sides of the membrane. During budding at an intracellular membrane, a short linear domain in the cytosolic preS region interacts with binding sites on the capsid surface. The virions are subsequently secreted into the blood. In addition, the surface proteins can bud in the absence of capsids and form subviral lipoprotein particles of 20 nm diameter which are also secreted.
文摘Background Non-invasive nasopharyngeal carcinoma （NPC） screening usually involves serological testing for the presence of IgA antibodies to Epstein-Barr virus （EBV） capsid antigen （VCA）. The present meta-analysis determined the accuracy of VCA-lgA in the diagnosis of NPC.Methods A systematic review of studies was conducted and data on the accuracy of VCA-lgA concentrations in the diagnosis of NPC were pooled using random effects models. Receiver operating characteristic curves were used to summarize the overall test performance. Results Twenty studies met the inclusion criteria for the meta-analysis. The summary estimates for VCA-lgA in the diagnosis of NPC were： sensitivity 0.91 （95% confidence interval （Cl）： 0.90-0.92）, specificity 0.92 （95% Cl： 0.92-0.93）, positive likelihood ratio 31.65 （95% Cl： 10.99-91.15）, negative likelihood ratio 0.10 （95% Cl： 0.07-0.13） and diagnostic odds ratio 414.59 （95% Cl： 174.96-982.42）. The area under the summary receiver operating characteristic curves was 0.98.Conclusion The sensitivity and the specificity of serum VCA-lgA are very high, suggesting that the presence of VCA-lgA in peripheral blood is a valuable predictor for NPC.
基金supported by the National Nature Science Foundation of China(No.81201285)Dr.Start-up Fund of Liaoning Province(No.20141134)+2 种基金excellent talents project in colleges and universities of the Liaoning Province Foundation(No.LJQ2015067)college students of science and technology innovation fund,Liaoning medical university principal fund(No.2014D09)approved by the ethics committees of Liao Yi[2014](NO.6-20150005)
文摘Dear Editor,Astrovirus is an enteric virus associated with sporadic diarrhea or large outbreaks of gastroenteritis（Mendez et al.,2013）.Until 2008,human astroviruses（HAst Vs）were classified into eight serotypes—HAstV-1 to HAstV-8—based on the reactivity of their capsid protein with type-specific antibodies.Among these serotypes,HAstV-1is the most prevalent globally.However,some divergent new astroviruses（MLB1/MLB2,VA1/VA2/VA3,
基金the National Natural Science Foundation of China,China(Grant Nos.81925036 and 81872814)the Key Research and Development Program of Science and Technology Department of Sichuan Province,China(Grant No.2020YFS0570)+1 种基金111 project,China(Grant No.B18035)the Fundamental Research Funds for the Central Universities,China。
文摘Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines,the epidemic prevention and control are still challenging.Here,we employ a capsid and antigen structure engineering(CASE)strategy to manufacture an adenoassociated viral serotype 6-based vaccine(S663V-RBD),which expresses trimeric receptor binding domain(RBD)of spike protein fused with a biological adjuvant RS09.Impressively,the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months.Compared to the licensed BBIBP-CorV(Sinopharm,China),a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type,C.37(Lambda)and B.1.617.2(Delta).More interestingly,the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid.Given its effectiveness,the CASE-based S663VRBD may provide a new solution for the current and next pandemic.
