CD8+T cell evasion mandates CD4+T cell control of chronic gamma-herpesvirus infection

Abstract

Gamma-herpesvirus infections are regulated by both CD4+and CD8+T cells. However clinical disease occurs mainly in CD4+T cell-deficient hosts. In CD4+T cell-deficient mice, CD8+T cells control acute but not chronic lung infection by Murid Herpesvirus-4 (MuHV-4). We show that acute and chronic lung infections differ in distribution: most acute infection was epithelial, whereas most chronic infection was in myeloid cells. CD8+T cells controlled epithelial infection, but CD4+T cells and IFNγ were required to control myeloid cell infection. Disrupting the MuHV-4 K3, which degrades MHC class I heavy chains, increased viral epitope presentation by infected lung alveolar macrophages and allowed CD8+T cells to prevent disease. Thus, viral CD8+T cell evasion led to niche-specific immune control, and an essential role for CD4+T cells in limiting chronic infection.