Crimean-Congo hemorrhagic fever virus(CCHFV)is a biosafety level-4(BSL-4)pathogen that causes Crimean-Congo hemorrhagic fever(CCHF)characterized by hemorrhagic manifestation,multiple organ failure and high mortality r...Crimean-Congo hemorrhagic fever virus(CCHFV)is a biosafety level-4(BSL-4)pathogen that causes Crimean-Congo hemorrhagic fever(CCHF)characterized by hemorrhagic manifestation,multiple organ failure and high mortality rate,posing great threat to public health.Despite the recently increasing research efforts on CCHFV,host cell responses associated with CCHFV infection remain to be further characterized.Here,to better understand the cellular response to CCHFV infection,we performed a transcriptomic analysis in human kidney HEK293 cells by high-throughput RNA sequencing(RNA-seq)technology.In total,496 differentially expressed genes(DEGs),including 361 up-regulated and 135 down-regulated genes,were identified in CCHFV-infected cells.These regulated genes were mainly involved in host processes including defense response to virus,response to stress,regulation of viral process,immune response,metabolism,stimulus,apoptosis and protein catabolic process.Therein,a significant up-regulation of type III interferon(IFN)signaling pathway as well as endoplasmic reticulum(ER)stress response was especially remarkable.Subsequently,representative DEGs from these processes were well validated by RT-qPCR,confirming the RNA-seq results and the typical regulation of IFN responses and ER stress by CCHFV.Furthermore,we demonstrate that not only type I but also type III IFNs(even at low dosages)have substantial anti-CCHFV activities.Collectively,the data may provide new and comprehensive insights into the virus-host interactions and particularly highlights the potential role of type III IFNs in restricting CCHFV,which may help inform further mechanistic delineation of the viral infection and development of anti-CCHFV strategies.展开更多
Emerging infectious diseases are major threats to human health.Most severe viral disease outbreaks occur in developing regions where health conditions are poor.With increased international travel and business,the poss...Emerging infectious diseases are major threats to human health.Most severe viral disease outbreaks occur in developing regions where health conditions are poor.With increased international travel and business,the possibility of eventually transmitting infectious viruses between different countries is increasing.The most effective approach in preventing viral diseases is vaccination.However,vaccines are not currently available for numerous viral diseases.Viruslike particles(VLPs) are engineered vaccine candidates that have been studied for decades.VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles.VLPs have antigenicity similar to that of the native virus,but are non-infectious as they lack key viral genetic material.VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines.Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses,which may offer effective antiviral protection.Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases.The infectious agents discussed include RNA viruses from different virus families,such as the Arenaviridae,Bunyaviridae,Caliciviridae,Coronaviridae,Filoviridae,Flaviviridae,Orthomyxoviridae,Paramyxoviridae,and Togaviridae families.展开更多
The newly emerged mosquito-borne Zika virus(ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including in...The newly emerged mosquito-borne Zika virus(ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles(VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies. In this study, we used a new strategy to produce ZIKV VLPs based on the baculovirus expression system and demonstrated the feasibility of their use as a vaccine candidate. The pre-membrane(prM) and envelope(E) proteins were co-expressed in insect cells and selfassembled into particles similar to ZIKV. We found that the ZIKV VLPs could be quickly and easily prepared in large quantities using this system. The VLPs were shown to have good immunogenicity in immunized mice, as they stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses. Thus, the baculovirus-based ZIKV VLP vaccine is a safe, effective and economical vaccine candidate for use against ZIKV.展开更多
基金supported by the National Key Research and Development Program of China(2018YFA0507202)the National Natural Science Foundation of China(32170171,31870162,and 82161138003)the Youth Innovation Promotion Association of Chinese Academy of Sciences.
文摘Crimean-Congo hemorrhagic fever virus(CCHFV)is a biosafety level-4(BSL-4)pathogen that causes Crimean-Congo hemorrhagic fever(CCHF)characterized by hemorrhagic manifestation,multiple organ failure and high mortality rate,posing great threat to public health.Despite the recently increasing research efforts on CCHFV,host cell responses associated with CCHFV infection remain to be further characterized.Here,to better understand the cellular response to CCHFV infection,we performed a transcriptomic analysis in human kidney HEK293 cells by high-throughput RNA sequencing(RNA-seq)technology.In total,496 differentially expressed genes(DEGs),including 361 up-regulated and 135 down-regulated genes,were identified in CCHFV-infected cells.These regulated genes were mainly involved in host processes including defense response to virus,response to stress,regulation of viral process,immune response,metabolism,stimulus,apoptosis and protein catabolic process.Therein,a significant up-regulation of type III interferon(IFN)signaling pathway as well as endoplasmic reticulum(ER)stress response was especially remarkable.Subsequently,representative DEGs from these processes were well validated by RT-qPCR,confirming the RNA-seq results and the typical regulation of IFN responses and ER stress by CCHFV.Furthermore,we demonstrate that not only type I but also type III IFNs(even at low dosages)have substantial anti-CCHFV activities.Collectively,the data may provide new and comprehensive insights into the virus-host interactions and particularly highlights the potential role of type III IFNs in restricting CCHFV,which may help inform further mechanistic delineation of the viral infection and development of anti-CCHFV strategies.
文摘Emerging infectious diseases are major threats to human health.Most severe viral disease outbreaks occur in developing regions where health conditions are poor.With increased international travel and business,the possibility of eventually transmitting infectious viruses between different countries is increasing.The most effective approach in preventing viral diseases is vaccination.However,vaccines are not currently available for numerous viral diseases.Viruslike particles(VLPs) are engineered vaccine candidates that have been studied for decades.VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles.VLPs have antigenicity similar to that of the native virus,but are non-infectious as they lack key viral genetic material.VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines.Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses,which may offer effective antiviral protection.Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases.The infectious agents discussed include RNA viruses from different virus families,such as the Arenaviridae,Bunyaviridae,Caliciviridae,Coronaviridae,Filoviridae,Flaviviridae,Orthomyxoviridae,Paramyxoviridae,and Togaviridae families.
基金supported by the Science and Technology Basic Work Program (2013FY113500) from the Ministry of Science and Technology of Chinathe strategic priority research program of the Chinese Academy of Sciences (ZDRW-ZS2016-4)
文摘The newly emerged mosquito-borne Zika virus(ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles(VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies. In this study, we used a new strategy to produce ZIKV VLPs based on the baculovirus expression system and demonstrated the feasibility of their use as a vaccine candidate. The pre-membrane(prM) and envelope(E) proteins were co-expressed in insect cells and selfassembled into particles similar to ZIKV. We found that the ZIKV VLPs could be quickly and easily prepared in large quantities using this system. The VLPs were shown to have good immunogenicity in immunized mice, as they stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses. Thus, the baculovirus-based ZIKV VLP vaccine is a safe, effective and economical vaccine candidate for use against ZIKV.