Nonstructural NS1 proteins of several mosquito-borne Flavivirus do not inhibit TLR3 signaling.
Flaviviruses are single-stranded positive RNA viruses that replicate through double stranded RNA (dsRNA) intermediates. These dsRNA may be recognized as pathogen-associated molecular patterns by cellular receptors including membrane-bound Toll-like receptor 3 (TLR3) and cytosolic helicases RIG-I and MDA5. dsRNA stimulation results in signaling cascades converging to activation of interferon (IFN) regulatory factor 3 (IRF3) and to transcriptional activation of several interferon stimulated genes, including IFNss and inflammatory cytokines. There are conflicting reports concerning the ability of West Nile virus to counteract TLR3 signaling. In our analyses, transiently or stably expressed NS1 proteins from two West Nile viruses, two dengue 2 viruses and a yellow fever virus failed to inhibit TLR3 signaling in two different mammalian cell lines. Moreover, using siRNA inhibiting the helicase signalization pathway, we show that viral infection did not impede TLR3 responses to poly(I:C). We conclude that NS1 proteins from distinct mosquito-borne flaviviruses do not inhibit TLR3 signaling.
Baronti
Cécile
C
UMR IRD 190, Emergence des Pathologies Virales, Université de la Méditerranée, Faculté de Médecine de la Timone, 27 Bd Jean Moulin, 13005 Marseille, France.
Sire
Joséphine
J
de Lamballerie
Xavier
X
Quérat
Gilles
G
D000818:Animals; D009033:Culicidae / Q000821:virology*; D005416:Flavivirus / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
C100315:NS1 protein, Flavivirus; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D017361:Viral Nonstructural Proteins