Myd88-dependent toll-like receptor 7 signaling mediates protection from severe Ross River virus-induced disease in mice
Autor(es): Neighbours Lauren M, Long Kristin, Whitmore Alan C, Heise Mark T
Resumo: Arthralgia-associated alphaviruses, including chikungunya virus (CHIKV) - Ross River virus (RRV), pose significant public health threats because of their ability to cause explosive outbreaks of debilitating arthralgia - myalgia in human populations. Although the host inflammatory response is known to contribute to the pathogenesis of alphavirus-induced arthritis - myositis, the role that Toll-like receptors (TLRs), which are major regulators of host antiviral - inflammatory responses, play in the pathogenesis of alphavirus-induced arthritis - myositis has not been extensively studied. Using a mouse model of RRV-induced myositis/arthritis, we found that myeloid differentiation primary response gene 88 (Myd88)-dependent TLR7 signaling is involved in protection from severe RRV-associated disease. Infections of Myd88- - TLR7-deficient mouse strains with RRV revealed that both Myd88 - TLR7 significantly contributed to protection from RRV-induced mortality, - both mouse strains exhibited more severe tissue damage than wild-type (WT) mice following RRV infection. While viral loads were unchanged in either Myd88 or TLR7 knockout mice compared to WT mice at early times postinfection, both Myd88 - TLR7 knockout mice exhibited higher viral loads than WT mice at late times postinfection. Furthermore, while high levels of RRV-specific antibody were produced in TLR7-deficient mice, this antibody had very little neutralizing activity - had lower affinity than WT antibody. Additionally, TLR7- - Myd88-deficient mice showed defects in germinal center activity, suggesting that TLR7-dependent signaling is critical for the development of protective antibody responses against RRV.
Imprenta: Journal of Virology, v. 86, n. 19, p. 10675-10685, 2012
Identificador do objeto digital: 10.1128/JVI.00601-12
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Public health
Data de publicação: 2012
