The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and...The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins;efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion(F) glycoprotein. The analysis of monoclonal antibody(mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein,which is a tetrameric oligomer,and not with soluble forms of G(sG) ,which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably,these mutants of G also appear to confer a post-receptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together,these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further,receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.展开更多
Background:The patients with Langya henipavirus(LayV)infection are managed mainly with symptomatic treatment and supportive care.Objective:This review article focuses on the beneficial effects of black seeds(Nigella s...Background:The patients with Langya henipavirus(LayV)infection are managed mainly with symptomatic treatment and supportive care.Objective:This review article focuses on the beneficial effects of black seeds(Nigella sativa)in the management of Langya henipavirus(LayV)infection.Methods:The literature was searched in online databases,including Medline/Pubmed/PMC,Google Scholar,Science Direct,Ebsco,Scopus,Web of Science,Embase,and reference lists,to identify published studies,which established beneficial effects of black seeds(N.sativa)related to signs and symptoms of LayV infection.Results:Black seeds(N.sativa)have shown potential antiviral,bronchodilatory,antihistaminic,antitussive,hepatoprotective,renoprotective,anti-inflammatory,antioxidant,and immunomodulatory properties in various clinical,animal,in-vitro,in-vivo,and in-silico studies,which would help the patients with LayV infection.Conclusion:N.sativa would be a potential herbal candidate in the management of LayV infection along with symptomatic treatment and supportive care,to prevent further deterioration,and hospitalization.The safety and efficacy of N.sativa in patients with LayV infection would further be established by future randomized controlled clinical trials.展开更多
Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis s...Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.展开更多
基金supported in part by NIH grant AI054715 to C.C.B.
文摘The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins;efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion(F) glycoprotein. The analysis of monoclonal antibody(mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein,which is a tetrameric oligomer,and not with soluble forms of G(sG) ,which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably,these mutants of G also appear to confer a post-receptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together,these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further,receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.
文摘Background:The patients with Langya henipavirus(LayV)infection are managed mainly with symptomatic treatment and supportive care.Objective:This review article focuses on the beneficial effects of black seeds(Nigella sativa)in the management of Langya henipavirus(LayV)infection.Methods:The literature was searched in online databases,including Medline/Pubmed/PMC,Google Scholar,Science Direct,Ebsco,Scopus,Web of Science,Embase,and reference lists,to identify published studies,which established beneficial effects of black seeds(N.sativa)related to signs and symptoms of LayV infection.Results:Black seeds(N.sativa)have shown potential antiviral,bronchodilatory,antihistaminic,antitussive,hepatoprotective,renoprotective,anti-inflammatory,antioxidant,and immunomodulatory properties in various clinical,animal,in-vitro,in-vivo,and in-silico studies,which would help the patients with LayV infection.Conclusion:N.sativa would be a potential herbal candidate in the management of LayV infection along with symptomatic treatment and supportive care,to prevent further deterioration,and hospitalization.The safety and efficacy of N.sativa in patients with LayV infection would further be established by future randomized controlled clinical trials.
基金supported by the National Natural Science Foundation of China International Cooperation and Exchange Program(8161101193)the National Science and Technology Major Project(2016ZX10004222)to G.Wong
文摘Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.
