K3-mediated evasion of CD8 + T cells aids amplification of a latent γ-herpesvirus

• Published in: Nature immunology Vol. 3; no. 8; pp. 733 - 740
• Main Authors: Stevenson, P.G, May, J.S, Smith, X.G, Marques, S, Adler, H, Koszinowski, U.H, Simas, J.P, Efstathiou, S
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.08.2002
• Subjects: 3T3 Cells; Animals; CD8-Positive T-Lymphocytes - immunology; Flow Cytometry; Gene Expression Regulation - immunology; Genes, MHC Class I - immunology; In Situ Hybridization; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mutagenesis, Insertional; Polymerase Chain Reaction; Rhadinovirus - genetics; Rhadinovirus - growth & development; Rhadinovirus - immunology; RNA, Viral - analysis; RNA, Viral - genetics; Spleen - virology; T-Lymphocytes, Cytotoxic - immunology; Transcription, Genetic - immunology; Viral Proteins - biosynthesis; Viral Proteins - genetics; Viral Proteins - immunology
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni818

The murine gamma-herpesvirus-68 (MHV-68) K3 protein, like that of the Kaposi's sarcoma associated herpesvirus, down-regulates major histocompatibility complex (MHC) class I expression. However, how this contributes to viral replication in vivo is unclear. After intranasal MHV-68 infection, K3 was transcribed both during acute lytic infection in the lung and during latency establishment in lymphoid tissue. K3-deficient viruses were not cleared more rapidly from the lung, but the number of latently infected spleen cells was reduced and the frequency of virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) was increased. CTL depletion reversed the viral latency deficit. Thus, a major function of K3 appears to be CTL evasion during viral latency expansion.