title: 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.
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland and Royal Children's Hospital, Brisbane, Australia.
authors.forename: Cindy S E
authors.initials: CSE
authors.lastname: Tan
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland and Royal Children's Hospital, Brisbane, Australia.
authors.forename: Clara
authors.initials: C
authors.lastname: Lawler
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland and Royal Children's Hospital, Brisbane, Australia.
authors.forename: Philip G
authors.identifier: http://orcid.org/0000-0002-3520-5060
authors.initials: PG
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018144:Rhadinovirus / Q000302:isolation & purification
chemical_list: D015395:Histocompatibility Antigens Class I