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  2. N Protein of Viral Hemorrhagic Septicemia Virus Suppresses STAT1-Mediated MHC Class II Transcription to Impair Antigen Presentation in Sea Perch, Lateolabrax japonicus

N Protein of Viral Hemorrhagic Septicemia Virus Suppresses STAT1-Mediated MHC Class II Transcription to Impair Antigen Presentation in Sea Perch, Lateolabrax japonicus

  • J Immunol. 2022 Mar 1;208(5):1076-1084. doi: 10.4049/jimmunol.2100939.
Xiaobing Lu 1 Wenxi Li 1 Jiasen Guo 1 Peng Jia 1 Wanwan Zhang 1 Meisheng Yi 2 Kuntong Jia 2
Affiliations

Affiliations

  • 1 School of Marine Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, Guangdong, China; and Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering Guangdong, Guangzhou, Guangdong, China.
  • 2 School of Marine Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, Guangdong, China; and Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering Guangdong, Guangzhou, Guangdong, China jiakt3@mail.sysu.edu.cn yimsh@mail.sysu.edu.cn.
Abstract

Upon virus invasion of the host, APCs process Ags to short Peptides for presentation by MHC class II (MHC-II). The recognition of virus-derived Peptides in the context of MHC-II by CD4+ T cells initiates the adaptive immune response for virus clearance. As a survival instinct, viruses have evolved mechanisms to evade Ag processing and presentation. In this study, we discovered that IFN-γ induced endogenous MHC-II expression by a sea perch brain cell line through the STAT1/IFN regulatory factor 1 (IRF1)/CIITA signaling pathway. Furthermore, viral hemorrhagic septicemia virus Infection significantly inhibited the IFN-γ-induced expression of IRF1, CIITA, MHC-II-α, and MHC-II-β genes. By contrast, although STAT1 transcript was upregulated, paradoxically, the STAT1 protein level was attenuated. Moreover, overexpression analysis revealed that viral hemorrhagic septicemia virus N protein blocked the IFN-γ-induced expression of IRF1, CIITA, MHC-II-α, and MHC-II-β genes, but not the STAT1 gene. We also found out that N protein interacted with STAT1 and enhanced the overall ubiquitination level of proteins, including STAT1 in Lateolabrax japonicus brain cells. Enhanced ubiquitination of STAT1 through K48-linked ubiquitination led to its degradation through the ubiquitin-proteasome pathway, thereby inhibiting the biological function of STAT1. Our study suggests that aquatic viruses target Ag presentation in lower vertebrates for immune evasion as do mammalian viruses.

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