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
Hendra virus,a novel member of the family Paramyxovirus that has emerged from bats in Australia,causes fatal disease in livestock and humans. Eleven spillover events have been identified since the first description of...Hendra virus,a novel member of the family Paramyxovirus that has emerged from bats in Australia,causes fatal disease in livestock and humans. Eleven spillover events have been identified since the first description of the virus in 1994,resulting in a total of 37 equine cases and six human cases. All human cases have been attributed to exposure to infected horses;there is no evidence of bat-to-human or human-to-human transmission. Low infectivity and a high case fatality rate are features of Hendra virus infection in both horses and humans. The temporal pattern of spillover events suggests seasonal factors(plausibly be environmental,biological or ecological) as the proximate triggers for spillover. Minimisation of the future occurrence and impact of Hendra virus infections requires an understanding of the ecology of flying foxes,of virus infection dynamics in flying foxes,and of the factors that promote spillover. Management strategies seek to minimize the opportunity for effective contact between bats and horses,and limit potential horse-to-horse and horse-to-human transmission. Incomplete knowledge of the ecology of the virus,of the proximate factors associated with spillover,and the inherent difficulties of effectively managing wild populations,preclude a management approach targeted at bats.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Hendra virus,a novel member of the family Paramyxovirus that has emerged from bats in Australia,causes fatal disease in livestock and humans. Eleven spillover events have been identified since the first description of the virus in 1994,resulting in a total of 37 equine cases and six human cases. All human cases have been attributed to exposure to infected horses;there is no evidence of bat-to-human or human-to-human transmission. Low infectivity and a high case fatality rate are features of Hendra virus infection in both horses and humans. The temporal pattern of spillover events suggests seasonal factors(plausibly be environmental,biological or ecological) as the proximate triggers for spillover. Minimisation of the future occurrence and impact of Hendra virus infections requires an understanding of the ecology of flying foxes,of virus infection dynamics in flying foxes,and of the factors that promote spillover. Management strategies seek to minimize the opportunity for effective contact between bats and horses,and limit potential horse-to-horse and horse-to-human transmission. Incomplete knowledge of the ecology of the virus,of the proximate factors associated with spillover,and the inherent difficulties of effectively managing wild populations,preclude a management approach targeted at bats.
