%0 Journal Article
%T A Single CD8+ T Cell Epitope Sets the Long-Term Latent Load of a Murid Herpesvirus
%A Sofia Marques
%A Marta Alenquer
%A Philip G. Stevenson
%A J. Pedro Simas
%J PLOS Pathogens
%D 2008
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1000177
%X 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¨Cassociated 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.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000177