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Inhibition of Translation Initiation by Protein 169: A Vaccinia Virus Strategy to
Suppress Innate and Adaptive Immunity and Alter Virus Virulence
#MMPMID26334635
Strnadova P
; Ren H
; Valentine R
; Mazzon M
; Sweeney TR
; Brierley I
; Smith GL
PLoS Pathog
2015[Sep]; 11
(9
): e1005151
PMID26334635
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Vaccinia virus (VACV) is the prototypic orthopoxvirus and the vaccine used to
eradicate smallpox. Here we show that VACV strain Western Reserve protein 169 is
a cytoplasmic polypeptide expressed early during infection that is excluded from
virus factories and inhibits the initiation of cap-dependent and cap-independent
translation. Ectopic expression of protein 169 causes the accumulation of 80S
ribosomes, a reduction of polysomes, and inhibition of protein expression
deriving from activation of multiple innate immune signaling pathways. A virus
lacking 169 (v?169) replicates and spreads normally in cell culture but is more
virulent than parental and revertant control viruses in intranasal and
intradermal murine models of infection. Intranasal infection by v?169 caused
increased pro-inflammatory cytokines and chemokines, infiltration of pulmonary
leukocytes, and lung weight. These alterations in innate immunity resulted in a
stronger CD8+ T-cell memory response and better protection against virus
challenge. This work illustrates how inhibition of host protein synthesis can be
a strategy for virus suppression of innate and adaptive immunity.
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