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RNF213 modulates γ-herpesvirus infection and reactivation via targeting the viral Replication and Transcription Activator

Huabin Tian,K. Yu,Liang He,Hongtao Xu,Chuanhui Han,Xiaolin Zhang,Xinlu Wang,Xuyuan Zhang,Liguo Zhang,G. Gao,H. Deng

Published 2023 in Proceedings of the National Academy of Sciences of the United States of America

ABSTRACT

Significance Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. Interferons play important roles in controlling KSHV replication. To explore the underlying mechanism, we screened a library of interferon-stimulated genes (ISGs) we previously built and identified RNF213, which suppresses gammaherpesvirus replication. RNF213 is the susceptibility gene for Moyamoya Disease in East Asians. Here, we found that RNF213 inhibits KSHV de novo infection and reactivation by down-regulating the expression of a virally encoded “molecular switch” protein named RTA. RNF213 interacts with RTA directly and promotes RTA ubiquitination and degradation through the ubiquitin–proteasome pathway. Our study uncovers the antiviral function of RNF213 and provides insights into understanding interferon-mediated host defense against herpesvirus infections.

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