Transition from inflammatory to anti-inflammatory immune responses in deer mice infected with Sin Nombre virus (105.20)

Abstract

Abstract Hantavirus cardiopulmonary syndrome (HCPS) is characterized by pronounced inflammation that is thought to contribute to its pathogenesis. Deer mice (Peromyscus maniculatus) are the principal reservoir hosts of Sin Nombre virus (SNV), the etiologic agent of the great majority of HCPS cases in North America. Deer mice have life-long apathogenic persistence with periods of viral shedding in excrement. Virus-specific CD4+ T cells from deer mice possess features of regulatory T cells at persistence. We examined the post-infection kinetics of viral load and immune gene expression in deer mice on days 2, 5, 7, 10, 15 and 20. Viral RNA peaked on day 10 in the lungs and day 15 in the heart, with decreased RNA correlating with the appearance of IgG on day 15. In spleens, Ccl3 and Ccl5 expression was elevated on day 2, while Ccl2 expression was elevated on days 7-15. Several inflammatory cytokine genes were elevated on days 5 and 7, including IL-12p35, IL-21 and IL-23, but then declined. TGFβ1 expression occurred early in infection, but markedly declined and reappeared on days 15 and 20. CD4 expression was elevated on day 7 while CD8 and TCRβ expression were elevated on days 7 and 10, perhaps reflecting a stalled antiviral T cell response. These data suggest that early in infection an inflammatory immune response occurs, but it transitions to an anti-inflammatory response. This switch may interfere with viral clearance and contribute to the persistence and ecology of SNV.