Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8.
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)-α1 and IFN-β 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.
Zhang
Tianzheng
T
TEDA School of Biological Sciences and Biotechnology, Nankai University, 23 Hongda Street, TEDA, Tianjin 300457, PR China.
Wang
Ying
Y
Zhang
Li
L
Liu
Bin
B
Xie
Jinhui
J
Wood
Charles
C
Wang
Jinzhong
J
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002522:Chlorocebus aethiops; D019288:Herpesvirus 8, Human / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014709:Vero Cells; D014775:Virus Activation; D014779:Virus Replication
C494234:IRF7 protein, human; D017874:Immediate-Early Proteins; D050839:Interferon Regulatory Factor-7; D012333:RNA, Messenger; D012367:RNA, Viral; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D008239:Lysine