Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus closely related to the human pathogens including yellow fever virus, dengue virus and West Nile virus. There are currently no effective antiviral therap...Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus closely related to the human pathogens including yellow fever virus, dengue virus and West Nile virus. There are currently no effective antiviral therapies for all of the flavivirus and only a few highly effective vaccines are licensed for human use. In this paper, the E protein domain III (DIII) of six heterologous flaviviruses (DENV1-4, WNV and JEV) was expressed in Escherichia coli successfully. The proteins were purified after a solubilization and refolding procedure, characterized by SDS-PAGE and Western blotting. Competitive inhibition showed that all recombinant flavivirus DIII proteins blocked the entry of JEV into BHK-21 cells. Further studies indicated that antibodies induced by the soluble recombinant flavivirus DIII partially protected mice against lethal JEV challenge. These results demonstrated that recombinant flavivirus DIII proteins could inhibit JEV infection competitively, and immunization with proper folding flavivirus DIII induced cross-protection against JEV infection in mice, implying a possible role of DIII for the cross-protection among flavivirus as well as its use in antigens for immunization in animal models.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the etiologic agent of the current coronavirus disease 2019(COVID-19)pandemic,has evolved to adapt to human host and transmission over the past 12 months.One...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the etiologic agent of the current coronavirus disease 2019(COVID-19)pandemic,has evolved to adapt to human host and transmission over the past 12 months.One prominent adaptive mutation is the asparagine-to-glycine substitution at amino acid position 614 in the viral spike protein(D614G),which has become dominant in the currently circulating virus strains.Since spike protein determines host ranges,tissue tropism,and pathogenesis through binding to the cellular receptor of angiotensin converting enzyme 2(ACE2),the D614G mutation is hypothesized to enhance viral fitness in human host,leading to increased transmission during the global pandemic.Here we summarize the recent progress on the role of the D614G mutation in viral replication,pathogenesis,transmission,and vaccine and therapeutic antibody development.These findings underscore the importance in closely monitoring viral evolution and defining their functions to ensure countermeasure efficacy against newly emerging variants.展开更多
Dear Editor The rapid evolution of SARS-CoV-2 mandates a better under-standing of cross-neutralization and cross-protection among variants.Such information is essential to guide vaccine strategy and public policy.To e...Dear Editor The rapid evolution of SARS-CoV-2 mandates a better under-standing of cross-neutralization and cross-protection among variants.Such information is essential to guide vaccine strategy and public policy.To examine the cross-protection among different variant spikes,we initially prepared four chimeric SARS-CoV-2 viruses(Fig.1a),each bearing the spike gene from Alpha,Beta,Gamma,or Epsilon in the backbone of USA-WA1/2020[isolated in January 2020 and defned as wild-type(WT)].展开更多
基金supported by Important National Science & Technology Specific Projects (2012ZX10004403, 2012ZX10004219)National Natural Scientific Fund of China (81072675)
文摘Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus closely related to the human pathogens including yellow fever virus, dengue virus and West Nile virus. There are currently no effective antiviral therapies for all of the flavivirus and only a few highly effective vaccines are licensed for human use. In this paper, the E protein domain III (DIII) of six heterologous flaviviruses (DENV1-4, WNV and JEV) was expressed in Escherichia coli successfully. The proteins were purified after a solubilization and refolding procedure, characterized by SDS-PAGE and Western blotting. Competitive inhibition showed that all recombinant flavivirus DIII proteins blocked the entry of JEV into BHK-21 cells. Further studies indicated that antibodies induced by the soluble recombinant flavivirus DIII partially protected mice against lethal JEV challenge. These results demonstrated that recombinant flavivirus DIII proteins could inhibit JEV infection competitively, and immunization with proper folding flavivirus DIII induced cross-protection against JEV infection in mice, implying a possible role of DIII for the cross-protection among flavivirus as well as its use in antigens for immunization in animal models.
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the etiologic agent of the current coronavirus disease 2019(COVID-19)pandemic,has evolved to adapt to human host and transmission over the past 12 months.One prominent adaptive mutation is the asparagine-to-glycine substitution at amino acid position 614 in the viral spike protein(D614G),which has become dominant in the currently circulating virus strains.Since spike protein determines host ranges,tissue tropism,and pathogenesis through binding to the cellular receptor of angiotensin converting enzyme 2(ACE2),the D614G mutation is hypothesized to enhance viral fitness in human host,leading to increased transmission during the global pandemic.Here we summarize the recent progress on the role of the D614G mutation in viral replication,pathogenesis,transmission,and vaccine and therapeutic antibody development.These findings underscore the importance in closely monitoring viral evolution and defining their functions to ensure countermeasure efficacy against newly emerging variants.
文摘Dear Editor The rapid evolution of SARS-CoV-2 mandates a better under-standing of cross-neutralization and cross-protection among variants.Such information is essential to guide vaccine strategy and public policy.To examine the cross-protection among different variant spikes,we initially prepared four chimeric SARS-CoV-2 viruses(Fig.1a),each bearing the spike gene from Alpha,Beta,Gamma,or Epsilon in the backbone of USA-WA1/2020[isolated in January 2020 and defned as wild-type(WT)].
