K3-mediated evasion of CD8(+) T cells aids amplification of a latent gamma-herpesvirus.
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.
Stevenson
P G
PG
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. pgs27@mole.bio.cam.ac.uk
May
J S
JS
Smith
X G
XG
Marques
S
S
Adler
H
H
Koszinowski
U H
UH
Simas
J P
JP
Efstathiou
S
S
D016475:3T3 Cells; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D005805:Genes, MHC Class I / Q000276:immunology; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016254:Mutagenesis, Insertional; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D018144:Rhadinovirus / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D013154:Spleen / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D012367:RNA, Viral; D014764:Viral Proteins