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PROJECT
SUMMARY
UPDATE:
Oscar graduated and has moved out to Lawrence Livermore up
near SF and currently works for Sandia.
Nipah
virus is a deadly virus that can cause death in up 70% of
infected patients, mostly from fatal inflammation of the brain.
Nipah virus emerged in peninsular Malaysia and Singapore in
1998-1999 when neurological and respiratory disease occurred
among agricultural and abattoir workers in close contact with
Nipah-infected pigs. Since then, other outbreaks have occurred
in various parts of Bangledesh with possible spread via human-to-human
transmission. Pteropid fruit bats are considered Nipah's natural
reservoir host and their habitat includes the regions between
eastern Africa, Southeast Asia and Australia. Nipah's re-emergence
in these geographical regions remains a potential threat.
Moreover, Nipah virus is considered a "priority pathogen"
for bioterrorism purposes, and it has the potential for widespread
economic devastation as it can spread rapidly among susceptible
livestock.
My project mainly focuses on Nipah's
interaction with its cellular receptors. We initially identified
the receptor that mediates Nipah virus entry into cells as
ephrinB2. This molecule is critical for the development of
the vascular and nervous system, and is highly expressed on
endothelial cells and neurons, which are also the two cell
types preferentially infected by Nipah virus in vivo.
EphrinB2 belongs to a large family
of related molecules that are variably conserved in structure
and function. When we screened all known human ephrins, we
found that a closely related molecule, ephrinB3, also can
function as an entry receptor for Nipah virus. In addition,
we established that while ephrinB2 was used more efficiently
than ephrinB3 as an entry receptor, the same two critical
amino acids in ephrinB2 and B3 were responsible for the viral
receptor activity of these molecules.
Recent gene expression studies
in the adult mouse brain (see Allen Brain Atlas) indicate
that ephrinB3, but not ephrinB2, is expressed in several regions
of the brain stem. A report on the clinical features of NiV
encelphalitis revealed that the main cause of death appeared
to involve severe neuronal dysfunction, particularly regions
of the brain stem. We hypothesize that the ability of NiV,
or the related Hendra virus, to use ephrinB3 may be a key
pathogenic determinant of fatal disease.
On a personal note, I have recently
finished my doctoral studies and have transitioned into a
temporary post-doc position while I finish up some projects
I have in the works and look for a more permanent position.
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