Lysine residues of interferon regulatory factor 7 affect the replication and transcription activatormediated lytic replication of Kaposi’s sarcomaassociated herpesvirus/human herpesvirus 8

Authors

Tianzheng Zhang, Nankai University
Ying Wang, Nankai University
Li Zhang, Nankai University
Bin Liu, Nankai University
Jinhui Xie, Nankai University
Charles Wood, University of Nebraska-LincolnFollow
Jinzhong Wang, Nankai University

Citation

Journal of General Virology (2011), 92, 181–187

Comments

Copyright 2011 SGM

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection goes through latent and lytic phases, which are controlled by the viral replication and transcription activator (RTA). Upon KSHV infection, the host responds by suppressing RTA-activated lytic gene expression through interferon regulatory factor 7 (IRF-7), a key regulator of host innate immune response. Lysine residues are potential sites for post-translational modification of IRF-7, and were suggested to be critical for its activity. In this study, we analysed the 15 lysine residues for their effects on IRF-7 function by site-directed mutagenesis. We found that some mutations affect the ability of IRF-7 to activate interferon (IFN)-a1 and IFN-b promoters, to suppress RTA-mediated lytic gene expression and to repress KSHV reactivation and lytic replication. However, other mutations affect only a subset of these four functions. These findings demonstrate that the lysine residues of IRF-7 play important roles in mediating IFN synthesis and modulating viral lytic replication.