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Published on: October 28, 2019
VZV IE4 downregulates cellular surface MHC-I via sequestering it to the Golgi complex
1College of Animal Science and Technology, Jiangxi Engineering Research Center for Animal Health Products, Jiangxi Agricultural University, Nanchang, Jiangxi, 330045, China.
None:
Varicella-zoster virus (VZV) infection downregulates surface major histocompatibility complex class I (MHC-I) expression and retains MHC-I in the Golgi complex of infected cells. However, the underlying mechanism is not fully understood. The VZV IE4 protein is a multifunctional protein that is essential for VZV infection. In this study, the human leucocyte antigen C (HLA-C) protein was identified as a novel cellular factor associated with IE4. Ectopically expressed IE4 co-localizes with HLA-C, sequesters HLA-C to the Golgi complex and downregulates cellular surface MHC-I. VZV, with a mutated Golgi localization signal in IE4, denoted as mutated IE4 (mIE4) VZV, was constructed. In mIE4 VZV-infected cells, the cellular surface MHC-I was restored, and HLA-C was not retained in the Golgi complex. In summary, for the first time, we demonstrate a novel role of VZV IE4 in interfering with the MHC-I presentation pathway, suggesting that it may contribute to the evasion of host antiviral adaptive immunity.
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