The Mechanism of Henipavirus Fusion:Examining the Relationships between the Attachment and Fusion Glycoproteins  

作　　者：Andrew C. Hickey Christopher C. Broder 

机构地区：[1]Department of Microbiology and Immunology,Uniformed Services University of the Health Sciences

出　　处：《Virologica Sinica》2009年第2期110-120,共11页中国病毒学（英文版）

基　　金：supported in part by NIH grant AI054715 to C.C.B.

摘　　要：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.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.

关 键 词：Hendra virus Nipah virus Henipavirus PARAMYXOVIRUS Viral entry 

分 类 号：Q939.4[生物学—微生物学]