Open AccessThe DNase of Gammaherpesviruses Impairs Recognition by Virus-Specific CD8+T Cells through an Additional Host Shutoff Function
Author(s) -
Jianmin Zuo,
Wendy A. Thomas,
Daphne van Leeuwen,
Jaap M. Middeldorp,
Emmanuel J. H. J. Wiertz,
Maaike E. Ressing,
Martin Rowe
Publication year - 2008
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01946-07
Subject(s) - biology , virus , cd8 , human leukocyte antigen , virology , gene , epstein–barr virus , genetics , microbiology and biotechnology , immune system , antigen
The DNase/alkaline exonuclease (AE) genes are well conserved in all herpesvirus families, but recent studies have shown that the AE proteins of gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) exhibit an additional function which shuts down host protein synthesis. One correlate of this additional shutoff function is that levels of cell surface HLA molecules are downregulated, raising the possibility that shutoff/AE genes of gammaherpesviruses might contribute to viral immune evasion. In this study, we show that both BGLF5 (EBV) and SOX (KSHV) shutoff/AE proteins do indeed impair the ability of virus-specific CD8+ T-cell clones to recognize endogenous antigen via HLA class I. Random mutagenesis of theBGLF5 gene enabled us to genetically separate the shutoff and AE functions and to demonstrate that the shutoff function was the critical factor determining whether BGLF5 mutants can impair T-cell recognition. These data provide further evidence that EBV has multiple mechanisms to modulate HLA class I-restricted T-cell responses, thus enabling the virus to replicate and persist in the immune-competent host.