Epstein-Barr virus LF2: an antagonist to type I interferon.
Upon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated antiviral pathway, which is mediated by IFN regulatory factors (IRFs). In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Despite its association with significant human health problems, activities of Epstein-Barr virus (EBV), a human tumor-inducing herpesvirus, to evade host IFN-mediated innate immunity have not been well characterized. To search for EBV genes that block IFN signal transduction, we carried out a screening of EBV open reading frames for their abilities to block IFN-alpha/beta-mediated luciferase expression upon Sendai virus infection. This screening demonstrates that EBV LF2 tegument protein specifically interacts with the central inhibitory association domain of IRF7, and this interaction leads to inhibition of the dimerization of IRF7, which suppresses IFN-alpha production and IFN-mediated immunity. This demonstrates a novel immune evasion mechanism of EBV LF2 in blocking cellular IRF7-mediated innate immunity.
Wu
Liguo
L
Department of Microbiology and Molecular Genetics, Tumor Virology Division, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
Fossum
Even
E
Joo
Chul Hyun
CH
Inn
Kyung-Soo
KS
Shin
Young Chul
YC
Johannsen
Eric
E
Hutt-Fletcher
Lindsey M
LM
Hass
Juergen
J
Jung
Jae U
JU
D002460:Cell Line; D017930:Genes, Reporter; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007370:Interferon Type I / Q000037:antagonists & inhibitors*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism*
C101688:BZLF2 protein, Herpesvirus 4, Human; D006023:Glycoproteins; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D014764:Viral Proteins; D008156:Luciferases