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PROJECT
SUMMARY
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 (JV).
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
(JV).
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.
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