Work

Basic Residues in the Matrix Domain and Multimerization Target Murine Leukemia Virus Gag to the Virological Synapse

Year: 2013

Type: article

Abstract: Murine leukemia virus (MLV) can efficiently spread in tissue cultures by polarizing assembly to virological synapses. The viral envelope glycoprotein (Env) establishes cell-cell contacts and subsequently recruits Gag by a process that depends on its cytoplasmic tail. MLV Gag is recruited to virological synapses through the matrix domain (MA) (J. Jin, F. Li, and W. Mothes, J. Virol. 85:7672-7682, 2011). However, how MA targets Gag to sites of cell-cell contact remains unknown. Here we report that basic residues within MA are critical for directing MLV Gag to virological synapses. Alternative membrane targeting domains (MTDs) containing multiple basic residues can efficiently substitute MA to direct polarized assembly. Similarly, mutations in the polybasic cluster of MA that disrupt Gag polarization can be rescued by N-terminal addition of MTDs containing basic residues. MTDs containing basic residues alone fail to be targeted to the virological synapse. Systematic deletion experiments reveal that domains within Gag known to mediate Gag multimerization are also required. Thus, our data predict the existence of a specific "acidic" interface at virological synapses that mediates the recruitment of MLV Gag via the basic cluster of MA and Gag multimerization.

Source: Journal of Virology

DOI: 10.1128/jvi.03263-12

Authors: Fei Li, Jing Jin, Christin Herrmann, Walther Mothes

Institution: Yale University

Language: English

Topic: T-cell and Retrovirus Studies

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: green

Funders: Pfizer, National Cancer Institute

Award: Retrovirus cell-to-cell transmission