Work

Cul3-KLHL20 E3 ubiquitin ligase plays a key role in the arms race between HIV-1 and host restriction

Year: 2021

Type: preprint

Abstract: HIV-1 must counteract various host restriction factors to establish productive infection. SERINC5 is a critical host restriction factor that potently blocks HIV-1 entry from virions, but its activity is counteracted by Nef. The SERINC5 and Nef activities are both initiated from the plasma membrane, where SERINC5 is packaged into virions and downregulated by Nef via lysosomal degradation. However, it is still unclear how SERINC5 is localized to the plasma membrane and how its expression is regulated on the plasma membrane. We now report that Cullin 3-KLHL20, a trans-Golgi network (TGN)-localized E3 ubiquitin ligase, polyubiquitinates SERINC5 at lysine 130 via K33- and K48-linked ubiquitin chains. The K130 polyubiquitination is required not only for the SERINC5 expression on the plasma membrane, but also the SERINC5 anti-HIV-1 activity and the Nef counteractive activity. Our study reveals an important role of K33/K48-branched ubiquitin chains in HIV-1 infection by regulating protein post-Golgi trafficking and degradation.

Source: Research Square

DOI: 10.21203/rs.3.rs-912958/v1

Authors: Rongrong Li, Iqbal Ahmad, Sunan Li, Silas Johnson, Liangliang Sun, Yong-Hui Zheng

Institutions: Chinese Academy of Agricultural Sciences, Harbin Veterinary Research Institute, ORCID, Michigan State University

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Allergy and Infectious Diseases