KSHV-encoded viral interferon regulatory factor 4 (vIRF4) interacts with IRF7 and inhibits interferon alpha production.
Before an infection can be completely established, the host immediately turns on the innate immune system through activating the interferon (IFN)-mediated antiviral pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) utilizes a unique antagonistic mechanism of type I IFN-mediated host antiviral immunity by incorporating four viral interferon regulatory factors (vIRF1-4). Herein, we characterized novel immune evasion strategies of vIRF4 to inhibit the IRF7-mediated IFN-α production. KSHV vIRF4 specifically interacts with IRF7, resulting in inhibition of IRF7 dimerization and ultimately suppresses IRF7-mediated activation of type I IFN. These results suggest that each of the KSHV vIRFs, including vIRF4, subvert IFN-mediated anti-viral response via different mechanisms. Therefore, it is indicated that KSHV vIRFs are indeed a crucial immunomodulatory component of their life cycles.
Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong 30019, Republic of Korea.
Sung-Woo
SW
Hwang
Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong 30019, Republic of Korea.
DongIk
D
Kim
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Zikha Neurogenic Institute, 1501 San Pablo Street, Los Angeles, CA 90089, USA.
Jae U
JU
Jung
Department of Biotechnology and Bioinformatics, College of Science and Technology, Korea University, Sejong 30019, Republic of Korea. Electronic address: leehr@korea.ac.kr.
Hye-Ra
HR
Lee
D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology*; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D029082:Sendai virus / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D014764:Viral Proteins; C413486:viral interferon regulatory factors; D008156:Luciferases
IFN-alpha; IRF7; Innate immunity; KSHV; vIRF4