Immune evasion proteins enhance cytomegalovirus latency in the lungs.

Institute for Virology, University Medical Center of Johannes Gutenberg University, 55131 Mainz, Germany.
Journal of Virology (Impact Factor: 5.08). 08/2009; 83(19):10293-8. DOI: 10.1128/JVI.01143-09
Source: PubMed

ABSTRACT CD8 T cells control cytomegalovirus (CMV) infection in bone marrow transplantation recipients and persist in latently infected lungs as effector memory cells for continuous sensing of reactivated viral gene expression. Here we have addressed the question of whether viral immunoevasins, glycoproteins that specifically interfere with antigen presentation to CD8 T cells, have an impact on viral latency in the murine model. The data show that deletion of immunoevasin genes in murine CMV accelerates the clearance of productive infection during hematopoietic reconstitution and leads to a reduced latent viral genome load, reduced latency-associated viral transcription, and a lower incidence of recurrence in lung explants.

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    ABSTRACT: Human cytomegalovirus (HCMV) interferes with MHC class I-restricted antigen presentation and thereby reduces recognition by CD8+ T cells. This interference is primarily mediated by ER-resident glycoproteins that are encoded in the US2-11 region of the viral genome. Such a suppression of recognition would be of particular importance immediately after infection, because several immunodominant viral antigens are already present in the cell in this phase. However, it is not known which of the evasion proteins gpUS2-11 interfere with antigen presentation to CD8+ T cells at this time of infection. Here we address this question, using recombinant viruses (RV) that express only one of the immunoevasins gpUS2, gpUS3, or gpUS11. Infection with RV-US3 had only a limited impact on the presentation of peptides from the CD8+ T cell antigens IE1 and pp65 under immediate-early conditions imposed by cycloheximide-actinomycin D blocking. Unexpectedly, both RV-US2 and RV-US11 considerably impaired the recognition of IE1 and pp65 by CD8+ T cells, and both US2 and, to lesser extent, US11 were transcribed under IE conditions. Thus, gpUS2 and gpUS11 are key effectors of MHC class I immune evasion immediately after HCMV infection.
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