Hepatitis B virus (HBV) infection is one of the major causes of liver diseases, affecting more than 350 million people worldwide. The interferon (IFN)-mediated innate immune responses could restrict HBV replication at...Hepatitis B virus (HBV) infection is one of the major causes of liver diseases, affecting more than 350 million people worldwide. The interferon (IFN)-mediated innate immune responses could restrict HBV replication at the different steps of viral life cycle. Indeed, IFN-α has been successfully used for treatment of patients with chronic hepatitis B. However, the role of the innate immune response in HBV replication and the mechanism of the anti-HBV effect of IFN-α are not completely explored. In this review, we summarized the currently available knowledge about the IFN-mediated anti-HBV effect in the HBV life cycle and the possible effectors downstream the IFN signaling pathway. The antiviral effect of Toll-like receptors (TLRs) in HBV replication is briefly discussed. The strategies exploited by HBV to evade the IFN- and TLR-mediated antiviral actions are summarized.展开更多
AIM To investigate the hepatitis C virus(HCV)infection in the tissues of carcinoma ofextrahepatic bile duct and study theircorrelation.METHODS HCV NS5 protein and HCV RNA weredetected by labeled streptavidin biotin(LS...AIM To investigate the hepatitis C virus(HCV)infection in the tissues of carcinoma ofextrahepatic bile duct and study theircorrelation.METHODS HCV NS5 protein and HCV RNA weredetected by labeled streptavidin biotin(LSAB)method and in situ reverse transcriptionpolymerase chain reaction(IS-RT-PCR)insections of 51 cases of carcinoma ofextrahepatic bile duct and 34 cases of controlgroup(without malignant biliary disease).RESULTS In 51 cases of carcinoma ofextrahepatic bile duct,HCV NS5 protein wasdetected in 14(27.5%),which was clearlystained in the cytoplasm of cancer cell but not inthe nucleus or cell membrane.HCV RNA wasdetected in 18(35.4%),which was located inthe nucleus of cancer cell in 12 cases and in thecytoplasm in 6 cases.HCV NS5 protein and RNAcoexistence was found in 2 cases.In 34 cases ofcontrol group,HCV RNA was detected in 2(5.9%).HCV NS5 protein and RNA positive cellswere found either scattered or in clusters.CONCLUSION The prevalence of hepatitis C viral infection in the tissues of carcinoma ofextrahepatic bile duct was significantly higherthan in control group(X^2=9.808,P=0.002).The findings suggest a correlation between HCVinfection and carcinoma of extrahepatic bileduct,which is different from the traditionalviewpoint.HCV infection might be involved inthe development of carcinoma of extrahepaticbile duct.展开更多
AIM: To investigate the transactivating effect of complete S protein of hepatitis B virus (HBV) and to construct a subtractive cDNA library of genes transactivated by complete S protein of HBV by suppression subtracti...AIM: To investigate the transactivating effect of complete S protein of hepatitis B virus (HBV) and to construct a subtractive cDNA library of genes transactivated by complete S protein of HBV by suppression subtractive hybridization (SSH) technique and to clone genes associated with its transactivation activity, and to pave the way for elucidating the pathogenesis of hepatitis B virus infection. METHODS: pcDNA3.1(-)-complete S containing full-length HBV S gene was constructed by insertion of HBV complete S gene into BamH I/Kpn I sites. HepG2 cells were cotransfected with pcDNA3.1(-)-complete S and pSV-lacZ. After 48 h, cells were collected and detected for the expression of β-galactosidase (β-gal). Suppression subtractive hybridization and bioinformatics techniques were used. The mRNA of HepG2 cells transfected with pcDNA3.Incomplete S and pcDNA3.1(-) empty vector was isolated, and detected for the expression of complete S protein by reverse transcription polymerase chain reaction (RT-PCR) method, and cDNA was synthesized. After digestion with restriction enzyme RsaI, cDNA fragments were obtained. Tester cDNA was then divided into two groups and ligated to the specific adaptors 1 and 2, respectively. After tester cDNA had been hybridized with driver cDNA twice and underwent nested PCR twice, amplified cDNA fragments were subcloned into pGEM-Teasy vectors to set up the subtractive library. Amplification of the library was carried out within E. coli strain DH5α. The cDNA was sequenced and analyzed in GenBank with BLAST search after polymerase chain reaction (PCR) amplification. RESULTS: The complete S mRNA could be detected by RT-PCR in HepG2 cells transfected with the pcDNA3.1(-)-complete S. The activity of β-gal in HepG2 cells transfected with the pcDNA3.1(-)-complete s was 6.9 times higher than that of control plasmid. The subtractive library of genes transactivated by HBV complete S protein was constructed successfully. The amplified library contains 86 positive clones. Colony PCR showed that 86 clones con展开更多
ISG20 is an interferon-inducible exonuclease that inhibits virus replication.Although ISG20 is thought to degrade viral RNA,the antiviral mechanism and specificity of ISG20 remain unclear.In this study,the antiviral r...ISG20 is an interferon-inducible exonuclease that inhibits virus replication.Although ISG20 is thought to degrade viral RNA,the antiviral mechanism and specificity of ISG20 remain unclear.In this study,the antiviral role of ovine ISG20(o ISG20)in bluetongue virus(BTV)infection was investigated.It was found that BTV infection upregulated the transcription of ovine ISG20(o ISG20)in a time-and BTV multiplicity of infection(MOI)-dependent manner.Overexpression of o ISG20 suppressed the production of BTV genome,proteins,and virus titer,whereas the knockdown of o ISG20 increased viral replication.o ISG20 was found to co-localize with BTV proteins VP4,VP5,VP6,and NS2,but only directly interacted with VP4.Exonuclease defective o ISG20 significantly decreased the inhibitory effect on BTV replication.In addition,the interaction of mutant o ISG20 and VP4 was weakened,suggesting that binding to VP4 was associated with the inhibition of BTV replication.The present data characterized the anti-BTV effect of o ISG20,and provides a novel clue for further exploring the inhibition mechanism of double-stranded RNA virus by ISG20.展开更多
The distribution of antibiotic resistance genes(ARGs)has been intensively studied in large-scale wastewater treatment plants and livestock sources.However,small-scale decentralized sewage treatment facilities must als...The distribution of antibiotic resistance genes(ARGs)has been intensively studied in large-scale wastewater treatment plants and livestock sources.However,small-scale decentralized sewage treatment facilities must also be explored due to their possible direct exposure to residents.In this study,six wastewater treatment facilities in developed rural areas in eastern China were investigated to understand their risks of spreading ARGs.Using metagenomics and network analysis tools,ARGs and bacterial and viral communities were identified in the influent(INF)and effluent(EFF)samples.The dominant ARGs belonged to the bacitracin class,which are different from most of municipal wastewater treatment plants(WWTPs).The dominant hosts of ARGs are Acidovorax in bacterial communities and Prymnesiovirus in viral communities.Furthermore,a positive relationship was found between ARGs and phages.The ARGs significantly correlated with phages were all hosted by specific genera of bacteria,indicating that phages had contributed to the ARG’s proliferation in sewage treatment facilities.Paying significant concern on the possible enhanced risks caused by bacteria,viruses and their related ARGs in decentralized sewage treatment facilities is necessary.展开更多
ORF virus (ORFV), the etiological agent of contagious pustular dermatitis in small ruminants, belongs to members of the genus Parapoxvirus of the Poxviridae. The genome of the ORFV is dsDNA of 139,962 bp which has abo...ORF virus (ORFV), the etiological agent of contagious pustular dermatitis in small ruminants, belongs to members of the genus Parapoxvirus of the Poxviridae. The genome of the ORFV is dsDNA of 139,962 bp which has about 89% coding region, 63% GC content and codes 130 proteins. There are four unique genes within the genome revealed by homology search of them two posses’ strong regulatory region and transmembrane helices. One of the ORF-039 contains signal peptide indicating the possibilities to be secretory protein coding gene. Comparative genomic analysis reveals significant differences in Bovine Papular Stomatitis Virus (BPSV) strain BV-AR02 and ORFV strain OV-SA00, and these may account for differences in host range. Interspecies sequence variability is observed in all functional classes of genes but is the highest in putative virulence/host range genes. Notably, ORFV contains genes which are homologous of Vaccinia virus. Phylogenetic analysis reveals that although divergent, ORFV virus is distinct from other known mammalian cowpox virus. An improved understanding of Parapoxvirus (PPV) biology will permit the engineering of novel vaccine viruses and expression vectors with enhanced efficacy and greater versatility. The novel vaccine will have a significant role in the economy of a country through the control of disease in an economically important and small ruminant caused by ORFV.展开更多
The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus,and it synchronizes the peripheral clocks in other tissues.Circadian clock genes and clock-contr...The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus,and it synchronizes the peripheral clocks in other tissues.Circadian clock genes and clock-controlled genes exist in almost all cell types.They have an essential role in many physiological processes,including lipid metabolism in the liver,regulation of the immune system,and the severity of infections.In addition,circadian rhythm genes can stimulate the immune response of host cells to virus infection.Hepatitis B virus(HBV)infection is the leading cause of liver disease and liver cancer globally.HBV infection depends on the host cell,and hepatocyte circadian rhythm genes are associated with HBV replication,survival,and spread.The core circadian rhythm proteins,REV-ERB and brain and muscle ARNTL-like protein 1,have a crucial role in HBV replication in hepatocytes.In addition to influencing the virus’s life cycle,the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines.Therefore,it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment.For these reasons,understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy.Therefore,this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.展开更多
基金Supported by National Natural Science Foundation of China to Pei RJ and Chen XC,Nos.31200135 and 31200699German Research Foundation to Lu MG,Nos.TRR60,GK1045/2 and GK1949
文摘Hepatitis B virus (HBV) infection is one of the major causes of liver diseases, affecting more than 350 million people worldwide. The interferon (IFN)-mediated innate immune responses could restrict HBV replication at the different steps of viral life cycle. Indeed, IFN-α has been successfully used for treatment of patients with chronic hepatitis B. However, the role of the innate immune response in HBV replication and the mechanism of the anti-HBV effect of IFN-α are not completely explored. In this review, we summarized the currently available knowledge about the IFN-mediated anti-HBV effect in the HBV life cycle and the possible effectors downstream the IFN signaling pathway. The antiviral effect of Toll-like receptors (TLRs) in HBV replication is briefly discussed. The strategies exploited by HBV to evade the IFN- and TLR-mediated antiviral actions are summarized.
文摘AIM To investigate the hepatitis C virus(HCV)infection in the tissues of carcinoma ofextrahepatic bile duct and study theircorrelation.METHODS HCV NS5 protein and HCV RNA weredetected by labeled streptavidin biotin(LSAB)method and in situ reverse transcriptionpolymerase chain reaction(IS-RT-PCR)insections of 51 cases of carcinoma ofextrahepatic bile duct and 34 cases of controlgroup(without malignant biliary disease).RESULTS In 51 cases of carcinoma ofextrahepatic bile duct,HCV NS5 protein wasdetected in 14(27.5%),which was clearlystained in the cytoplasm of cancer cell but not inthe nucleus or cell membrane.HCV RNA wasdetected in 18(35.4%),which was located inthe nucleus of cancer cell in 12 cases and in thecytoplasm in 6 cases.HCV NS5 protein and RNAcoexistence was found in 2 cases.In 34 cases ofcontrol group,HCV RNA was detected in 2(5.9%).HCV NS5 protein and RNA positive cellswere found either scattered or in clusters.CONCLUSION The prevalence of hepatitis C viral infection in the tissues of carcinoma ofextrahepatic bile duct was significantly higherthan in control group(X^2=9.808,P=0.002).The findings suggest a correlation between HCVinfection and carcinoma of extrahepatic bileduct,which is different from the traditionalviewpoint.HCV infection might be involved inthe development of carcinoma of extrahepaticbile duct.
基金Supported by the National Natural Science Foundation of China, No. C03011402, No. C30070690 the Science and Technique Foundation of PLA during the 9th Five-year Plan period, No. 98D063the Launching Foundation for Students Studying Abroad of PLA, No. 98H038the Youth Science and Technique Foundation of PLA during the 10th Five-year plan period, No. 01Q138the Science and Technique Foundation of PLA during the 10th Five-year Plan period, No. 01MB135
文摘AIM: To investigate the transactivating effect of complete S protein of hepatitis B virus (HBV) and to construct a subtractive cDNA library of genes transactivated by complete S protein of HBV by suppression subtractive hybridization (SSH) technique and to clone genes associated with its transactivation activity, and to pave the way for elucidating the pathogenesis of hepatitis B virus infection. METHODS: pcDNA3.1(-)-complete S containing full-length HBV S gene was constructed by insertion of HBV complete S gene into BamH I/Kpn I sites. HepG2 cells were cotransfected with pcDNA3.1(-)-complete S and pSV-lacZ. After 48 h, cells were collected and detected for the expression of β-galactosidase (β-gal). Suppression subtractive hybridization and bioinformatics techniques were used. The mRNA of HepG2 cells transfected with pcDNA3.Incomplete S and pcDNA3.1(-) empty vector was isolated, and detected for the expression of complete S protein by reverse transcription polymerase chain reaction (RT-PCR) method, and cDNA was synthesized. After digestion with restriction enzyme RsaI, cDNA fragments were obtained. Tester cDNA was then divided into two groups and ligated to the specific adaptors 1 and 2, respectively. After tester cDNA had been hybridized with driver cDNA twice and underwent nested PCR twice, amplified cDNA fragments were subcloned into pGEM-Teasy vectors to set up the subtractive library. Amplification of the library was carried out within E. coli strain DH5α. The cDNA was sequenced and analyzed in GenBank with BLAST search after polymerase chain reaction (PCR) amplification. RESULTS: The complete S mRNA could be detected by RT-PCR in HepG2 cells transfected with the pcDNA3.1(-)-complete S. The activity of β-gal in HepG2 cells transfected with the pcDNA3.1(-)-complete s was 6.9 times higher than that of control plasmid. The subtractive library of genes transactivated by HBV complete S protein was constructed successfully. The amplified library contains 86 positive clones. Colony PCR showed that 86 clones con
基金the National Key Research and Development Program of China(2021YFD18005022017YFD0502304)+2 种基金National Natural Science Foundation of China(31672562)NBCITS(CARS-37)ASTIP(CAAS-ASTIP-2016-LVRI)。
文摘ISG20 is an interferon-inducible exonuclease that inhibits virus replication.Although ISG20 is thought to degrade viral RNA,the antiviral mechanism and specificity of ISG20 remain unclear.In this study,the antiviral role of ovine ISG20(o ISG20)in bluetongue virus(BTV)infection was investigated.It was found that BTV infection upregulated the transcription of ovine ISG20(o ISG20)in a time-and BTV multiplicity of infection(MOI)-dependent manner.Overexpression of o ISG20 suppressed the production of BTV genome,proteins,and virus titer,whereas the knockdown of o ISG20 increased viral replication.o ISG20 was found to co-localize with BTV proteins VP4,VP5,VP6,and NS2,but only directly interacted with VP4.Exonuclease defective o ISG20 significantly decreased the inhibitory effect on BTV replication.In addition,the interaction of mutant o ISG20 and VP4 was weakened,suggesting that binding to VP4 was associated with the inhibition of BTV replication.The present data characterized the anti-BTV effect of o ISG20,and provides a novel clue for further exploring the inhibition mechanism of double-stranded RNA virus by ISG20.
基金supported by the Major Science and Technology Program for Water Pollution Control and Treatment(2017ZX07202-003)National Natural Science Foundation of China(51778325)+1 种基金the Fundamental Research Fund for the Central Universities(FRF-TP-20-011A)the Research Fund Program of Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology(2020B 1212060022).
文摘The distribution of antibiotic resistance genes(ARGs)has been intensively studied in large-scale wastewater treatment plants and livestock sources.However,small-scale decentralized sewage treatment facilities must also be explored due to their possible direct exposure to residents.In this study,six wastewater treatment facilities in developed rural areas in eastern China were investigated to understand their risks of spreading ARGs.Using metagenomics and network analysis tools,ARGs and bacterial and viral communities were identified in the influent(INF)and effluent(EFF)samples.The dominant ARGs belonged to the bacitracin class,which are different from most of municipal wastewater treatment plants(WWTPs).The dominant hosts of ARGs are Acidovorax in bacterial communities and Prymnesiovirus in viral communities.Furthermore,a positive relationship was found between ARGs and phages.The ARGs significantly correlated with phages were all hosted by specific genera of bacteria,indicating that phages had contributed to the ARG’s proliferation in sewage treatment facilities.Paying significant concern on the possible enhanced risks caused by bacteria,viruses and their related ARGs in decentralized sewage treatment facilities is necessary.
文摘ORF virus (ORFV), the etiological agent of contagious pustular dermatitis in small ruminants, belongs to members of the genus Parapoxvirus of the Poxviridae. The genome of the ORFV is dsDNA of 139,962 bp which has about 89% coding region, 63% GC content and codes 130 proteins. There are four unique genes within the genome revealed by homology search of them two posses’ strong regulatory region and transmembrane helices. One of the ORF-039 contains signal peptide indicating the possibilities to be secretory protein coding gene. Comparative genomic analysis reveals significant differences in Bovine Papular Stomatitis Virus (BPSV) strain BV-AR02 and ORFV strain OV-SA00, and these may account for differences in host range. Interspecies sequence variability is observed in all functional classes of genes but is the highest in putative virulence/host range genes. Notably, ORFV contains genes which are homologous of Vaccinia virus. Phylogenetic analysis reveals that although divergent, ORFV virus is distinct from other known mammalian cowpox virus. An improved understanding of Parapoxvirus (PPV) biology will permit the engineering of novel vaccine viruses and expression vectors with enhanced efficacy and greater versatility. The novel vaccine will have a significant role in the economy of a country through the control of disease in an economically important and small ruminant caused by ORFV.
文摘The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus,and it synchronizes the peripheral clocks in other tissues.Circadian clock genes and clock-controlled genes exist in almost all cell types.They have an essential role in many physiological processes,including lipid metabolism in the liver,regulation of the immune system,and the severity of infections.In addition,circadian rhythm genes can stimulate the immune response of host cells to virus infection.Hepatitis B virus(HBV)infection is the leading cause of liver disease and liver cancer globally.HBV infection depends on the host cell,and hepatocyte circadian rhythm genes are associated with HBV replication,survival,and spread.The core circadian rhythm proteins,REV-ERB and brain and muscle ARNTL-like protein 1,have a crucial role in HBV replication in hepatocytes.In addition to influencing the virus’s life cycle,the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines.Therefore,it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment.For these reasons,understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy.Therefore,this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.