A single CD8+ T cell epitope sets the long-term latent load of a murid herpesvirus.
The pathogenesis of persistent viral infections depends critically on long-term viral loads. Yet what determines these loads is largely unknown. Here, we show that a single CD8+ T cell epitope sets the long-term latent load of a lymphotropic gamma-herpesvirus, Murid herpesvirus-4 (MuHV-4). The MuHV-4 M2 latency gene contains an H2-Kd -restricted T cell epitope, and wild-type but not M2(-) MuHV-4 was limited to very low level persistence in H2d mice. Mutating the epitope anchor residues increased viral loads and re-introducing the epitope reduced them again. Like the Kaposi's sarcoma-associated herpesvirus K1, M2 shows a high frequency of non-synonymous mutations, suggesting that it has been selected for epitope loss. In vivo competition experiments demonstrated directly that epitope presentation has a major impact on viral fitness. Thus, host MHC class I and viral epitope expression interact to set the long-term virus load.
Instituto de Microbiologia e Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Sofia
S
Marques
Marta
M
Alenquer
Philip G
PG
Stevenson
J Pedro
JP
Simas
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D041681:NIH 3T3 Cells; D018144:Rhadinovirus / Q000235:genetics / Q000276:immunology*; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology*; D019562:Viral Load
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I