title: Basic residues in the matrix domain and multimerization target murine leukemia virus Gag to the virological synapse.
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.
authors.affiliation: Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Christin
authors.initials: C
authors.lastname: Herrmann
authors.forename: Walther
authors.initials: W
authors.lastname: Mothes
mesh_terms: D000818:Animals; D002460:Cell Line; D015683:Gene Products, gag / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D055503:Protein Multimerization; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D015683:Gene Products, gag; D014759:Viral Envelope Proteins