Cooperation between Epstein-Barr Virus Immune Evasion Proteins Spreads Protection from CD8 T Cell Recognition across All Three Phases of the Lytic Cycle

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Epstein Barr Virus (EBV), an oncogenic herpesvirus, infects and persists asymptomatically in the majority of humans. In immunocompetent individuals, EBV co-exists with its host as a lifelong infection in the face of strong anti-viral CD8+ T-cell responses. Evasion of this immune-response is presumed to be due in part to immune-modulating mechanisms of certain EBV-encoded proteins expressed during lytic cycle replication. Three such proteins (BNLF2a, BGLF5 and BILF1) have been identified biochemically as able to interfere with HLA-class I antigen presentation. In this study we investigated these proteins in the context of EBV-infected cells in lytic cycle, and their functional recognition by EBV virus-specific CD8+ T-cells. A novel feature of EBV biology was revealed; rather than demonstrating simple redundancy, evasion proteins effect optimum temporal protection at different phases of lytic cycle. BNLF2a strongly inhibited CD8+ T-cell recognition immediately after the EBV-infected cells entered lytic cycle, with its influence waning upon progression to later phases of lytic cycle. Conversely, BILF1 strongly inhibited recognition predominantly at the late phase of lytic cycle. Unexpectedly, despite its well-characterised molecular functions, BGLF5 had relatively little effect on recognition at any stage of lytic cycle. Our results help to explain the previously-identified unusual pattern of immunodominance of anti-EBV CD8+ T-cell responses.

Vyšlo v časopise: Cooperation between Epstein-Barr Virus Immune Evasion Proteins Spreads Protection from CD8 T Cell Recognition across All Three Phases of the Lytic Cycle. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004322
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004322

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