title: Multiple Gag domains contribute to selective recruitment of murine leukemia virus (MLV) Env to MLV virions.
abstract: Retroviruses, like all enveloped viruses, must incorporate viral glycoproteins to form infectious particles. Interactions between the glycoprotein cytoplasmic tail and the matrix domain of Gag are thought to direct recruitment of glycoproteins to native virions for many retroviruses. However, retroviruses can also incorporate glycoproteins from other viruses to form infectious virions known as pseudotyped particles. The glycoprotein murine leukemia virus (MLV) Env can readily form pseudotyped particles with many retroviruses, suggesting a generic mechanism for recruitment. Here, we sought to identify which components of Gag, particularly the matrix domain, contribute to recruitment of MLV Env into retroviral particles. Unexpectedly, we discovered that the matrix domain of HIV-1 Gag is dispensable for generic recruitment, since it could be replaced with a nonviral membrane-binding domain without blocking active incorporation of MLV Env into HIV virions. However, MLV Env preferentially assembles with MLV virions. When MLV and HIV particles are produced from the same cell, MLV Env is packaged almost exclusively by MLV particles, thus preventing incorporation into HIV particles. Surprisingly, the matrix domain of MLV Gag is not required for this selectivity, since MLV Gag containing the matrix domain from HIV is still able to outcompete HIV particles for MLV Env. Although MLV Gag is sufficient for selective incorporation to occur, no single Gag domain dictates the selectivity. Our findings indicate that Env recruitment is more complex than previously believed and that Gag assembly/budding sites have fundamental properties that affect glycoprotein incorporation.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri, USA.
authors.forename: Devon A
authors.initials: DA
authors.lastname: Gregory
authors.forename: Terri D
authors.initials: TD
authors.lastname: Lyddon
authors.forename: Marc C
authors.initials: MC
authors.lastname: Johnson
mesh_terms: D002460:Cell Line; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology*; D011485:Protein Binding; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism*; D019065:Virus Assembly
chemical_list: D015683:Gene Products, gag; D014759:Viral Envelope Proteins