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2016 ; 7
(ä): 751
Nephropedia Template TP
gab.com Text
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English Wikipedia
Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central
Nervous System Infections of Rabies Virus
#MMPMID27242764
Zhang D
; He F
; Bi S
; Guo H
; Zhang B
; Wu F
; Liang J
; Yang Y
; Tian Q
; Ju C
; Fan H
; Chen J
; Guo X
; Luo Y
Front Microbiol
2016[]; 7
(ä): 751
PMID27242764
show ga
Rabies remains a major public health concern in many developing countries. The
precise neuropathogenesis of rabies is unknown, though it is hypothesized to be
due to neuronal death or dysfunction. Mice that received intranasal inoculation
of an attenuated rabies virus (RABV) strain HEP-Flury exhibited subtle clinical
signs, and eventually recovered, which is different from the fatal encephalitis
caused by the virulent RABV strain CVS-11. To understand the neuropathogenesis of
rabies and the mechanisms of viral clearance, we applied RNA sequencing (RNA-Seq)
to compare the brain transcriptomes of normal mice vs. HEP-Flury or CVS-11
intranasally inoculated mice. Our results revealed that both RABV strains altered
positively and negatively the expression levels of many host genes, including
genes associated with innate and adaptive immunity, inflammation and cell death.
It is found that HEP-Flury infection can activate the innate immunity earlier
through the RIG-I/MDA-5 signaling, and the innate immunity pre-activated by
HEP-Flury or Newcastle disease virus (NDV) infection can effectively prevent the
CVS-11 to invade central nervous system (CNS), but fails to clear the CVS-11
after its entry into the CNS. In addition, following CVS-11 infection, genes
implicated in cell adhesion, blood vessel morphogenesis and coagulation were
mainly up-regulated, while the genes involved in synaptic transmission and ion
transport were significantly down-regulated. On the other hand, several genes
involved in the MHC class II-mediated antigen presentation pathway were activated
to a greater extent after the HEP-Flury infection as compared with the CVS-11
infection suggesting that the collaboration of CD4(+) T cells and MHC class
II-mediated antigen presentation is critical for the clearance of attenuated RABV
from the CNS. The differentially regulated genes reported here are likely to
include potential therapeutic targets for expanding the post-exposure treatment
window for RABV infection.