Structural Insight into HIV-1 Restriction by MxB

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2014 Oct 15

PMID 25312384

Citations 81

Authors

Jennifer L Fribourgh

Henry C Nguyen

Kenneth A Matreyek

Frances Joan D Alvarez

Brady J Summers

Tamaria G Dewdney

Christopher Aiken

Peijun Zhang

Alan Engelman

Yong Xiong

Affiliations

Soon will be listed here.

Abstract

The myxovirus resistance (Mx) proteins are interferon-induced dynamin GTPases that can inhibit a variety of viruses. Recently, MxB, but not MxA, was shown to restrict HIV-1 by an unknown mechanism that likely occurs in close proximity to the host cell nucleus and involves the viral capsid. Here, we present the crystal structure of MxB and reveal determinants involved in HIV-1 restriction. MxB adopts an extended antiparallel dimer and dimerization, but not higher-ordered oligomerization, is critical for restriction. Although MxB is structurally similar to MxA, the orientation of individual domains differs between MxA and MxB, and their antiviral functions rely on separate determinants, indicating distinct mechanisms for virus inhibition. Additionally, MxB directly binds the HIV-1 capsid, and this interaction depends on dimerization and the N terminus of MxB as well as the assembled capsid lattice. These insights establish a framework for understanding the mechanism by which MxB restricts HIV-1.

Citing Articles

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