Structural Insights into Semiliki Forest Virus Receptor Binding Modes Indicate Novel Mechanism of Virus Endocytosis

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2024 Dec 20

PMID 39705215

Authors

Decheng Yang

Nan Wang

Bingchen Du

Zhenzhao Sun

Shida Wang

Xijun He

JinYue Wang

Tao Zheng

Yutao Chen

Xiangxi Wang

Jingfei Wang

Affiliations

Soon will be listed here.

Abstract

The Very Low-Density Lipoprotein Receptor (VLDLR) is an entry receptor for the prototypic alphavirus Semliki Forest Virus (SFV). However, the precise mechanisms underlying the entry of SFV into cells mediated by VLDLR remain unclear. In this study, we found that of the eight class A (LA) repeats of the VLDLR, only LA2, LA3, and LA5 specifically bind to the native SFV virion while synergistically promoting SFV cell attachment and entry. Furthermore, the multiple cryo-electron microscopy structures of VLDLR-SFV complexes and mutagenesis studies have demonstrated that under physiological conditions, VLDLR primarily binds to E1-DIII of site-1, site-2, and site-1' at the twofold symmetry axes of SFV virion through LA2, LA3, and LA5, respectively. These findings unveil a novel mechanism for viral entry mediated by receptors, suggesting that conformational transitions in VLDLR induced by multivalent binding of LAs facilitate cellular internalization of SFV, with significant implications for the design of antiviral therapeutics.

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