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

Gamma-herpesvirus infections are regulated by both CD4and CD8T cells. However clinical disease occurs mainly in CD4T cell-deficient hosts. In CD4T cell-deficient mice, CD8T 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. CD8T cells controlled epithelial infection, but CD4T 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 CD8T cells to prevent disease. Thus, viral CD8T cell evasion led to niche-specific immune control, and an essential role for CD4T cells in limiting chronic infection