The EBV immunoevasins vIL-10 and BNLF2a protect newly infected B cells from immune recognition and elimination

• Published in: PLoS pathogens 2012-05, Vol.8 (5), p.e1002704-e1002704
• Main Authors: Jochum, Simon, Moosmann, Andreas, Lang, Stephan, Hammerschmidt, Wolfgang, Zeidler, Reinhard
• Format: Article
• Language: English
• Subjects: Antigen Presentation - immunology; Antigens, Viral - immunology; ATP-Binding Cassette Transporters - antagonists & inhibitors; B cells; Biology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - immunology; Epstein-Barr virus; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - metabolism; Epstein-Barr Virus Infections - virology; Genes; Health aspects; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - immunology; Herpesvirus 4, Human - metabolism; Herpesvirus 4, Human - pathogenicity; Humans; Immune Evasion; Immune system; Immunogenicity; Infections; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukins; Killer Cells, Natural - immunology; Killer Cells, Natural - virology; Medical research; Medicine; Microbiology; Physiological aspects; Proteins; Trans-Activators - biosynthesis; Viral Matrix Proteins - genetics; Viral Matrix Proteins - metabolism; Viral Proteins - genetics; Viral Proteins - metabolism; Virulence (Microbiology); Virus Latency
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1002704

Lifelong persistence of Epstein-Barr virus (EBV) in infected hosts is mainly owed to the virus' pronounced abilities to evade immune responses of its human host. Active immune evasion mechanisms reduce the immunogenicity of infected cells and are known to be of major importance during lytic infection. The EBV genes BCRF1 and BNLF2a encode the viral homologue of IL-10 (vIL-10) and an inhibitor of the transporter associated with antigen processing (TAP), respectively. Both are known immunoevasins in EBV's lytic phase. Here we describe that BCRF1 and BNLF2a are functionally expressed instantly upon infection of primary B cells. Using EBV mutants deficient in BCRF1 and BNLF2a, we show that both factors contribute to evading EBV-specific immune responses during the earliest phase of infection. vIL-10 impairs NK cell mediated killing of infected B cells, interferes with CD4+ T-cell activity, and modulates cytokine responses, while BNLF2a reduces antigen presentation and recognition of newly infected cells by EBV-specific CD8+ T cells. Together, both factors significantly diminish the immunogenicity of EBV-infected cells during the initial, pre-latent phase of infection and may improve the establishment of a latent EBV infection in vivo.