October 06, 2006
The emerging deadly Nipah virus: membrane fusion and viral entry
Nipah virus (NiV), along with its relative, Hendra virus, is the most deadly virus in the Paramyxovirus family. The Nipah virus emerged relatively recently, and it is a negative single-stranded RNA virus that can cause up to 75% mortality rate in humans and also infects economically important livestock. NiV can infect microvascular endothelial cells and neurons, among other cell types, and signs of human-to-human transmission have been observed in the recent Bangladesh epidemics. The Nipah virus contains two
envelope glycoproteins; the G attachment glycoprotein, which binds to the cell receptor, recently discovered in our laboratory to be EphrinB2, and the F fusion protein, which carries out membrane-to-membrane fusion during viral entry, after the attachment protein binding to the receptor occurs. My research focuses on the intricate mechanisms of viral fusion and viral entry into cells, as well as cell-cell fusion caused by viral glycoproteins, in particular those of the Nipah virus. Such research comprises the roles of amino-acid sequences as well as N-glycans and/or other secondary modifications, primarily in the fusion protein, but also in the attachment glycoprotein, with respect to the membrane fusion process. For example, we have shown that N-glycans in the F protein are involved in protecting the virus against antibody neutralization, at the cost of reducing fusion and
viral entry (Virology). We have also shown that F and G proteins interact with each other (JI), and that the N-glycans affect the avidity of the F and G interactions (Virology). Current studies focus on the roles of the cytoplasmic tail of the Nipah virus fusion protein in fusion, assembly, and viral entry processes, as well as in regulating the conformation of the fusion glycoprotein. The conformational differences in the F and G proteins post-receptor binding are being measured by the use of novel conformational antibodies as well as other methods.
Other articles of interest: Negrete et. al., 2005. Aguilar et. al., 2006.
Levroney, Aguilar et. al., 2006.
My URL address: http://mikewolf.bol.ucla.edu/LeeLab/HectorAg.htm
My department's URL address: http://www.mimg.ucla.edu/