Endogenous retroviruses provide protection against vaginal HSV-2 disease in mice.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B172
Abstract ID: 4440

Presenting Author:
Maria Tokuyama , Assistant Professor at Univ. of British Columbia

Abstract:

Endogenous retroviruses (ERVs) are genomic sequences that originated from ancient retroviral integration events. Both beneficial and detrimental functions have been attributed to ERVs in health and disease, but whether and how ERVs contribute to antiviral immunity is not well understood. Here, we used herpes simplex virus type 2 (HSV-2) to study the role of ERVs during acute viral infection in mice. We monitored HSV-2 infection and disease in Toll-like receptor 7-deficient (Tlr7-/-) mice that express high levels of infectious ERVs systemically compared to wildtype C57BL/6 mice and found that Tlr7-/- mice are protected from intravaginal HSV-2 infection. We then deleted the endogenous ecotropic murine leukemia virus (Emv2) locus, encoding the infectious ERV sequence, on the Tlr7-/- background to generate Emv2-/-Tlr7-/- mice. Emv2-/-Tlr7-/- mice lost protection against HSV-2, suggesting a direct role of Emv2-encoded ERVs in the protection against HSV-2 in Tlr7-/- mice. Intravaginal application of purified ERVs prior to HSV-2 infection delays disease in both wildtype and interferon-alpha receptor-deficient (Ifnar1-/-) mice. We did not observe enhanced type I interferon (IFN-I) signaling in the vaginal tissues of protected mice, but instead found enrichment in genes associated with extracellular matrix (ECM) organization. Together, our results revealed that ERVs modulate the ECM in the vaginal epithelium and protect mice against vaginal HSV-2 infection and disease.