title: Pseudotyping incompatibility between HIV-1 and gibbon ape leukemia virus Env is modulated by Vpu.
abstract: The Env protein from gibbon ape leukemia virus (GaLV) has been shown to be incompatible with human immunodeficiency virus type 1 (HIV-1) in the production of infectious pseudotyped particles. This incompatibility has been mapped to the C-terminal cytoplasmic tail of GaLV Env. Surprisingly, we found that the HIV-1 accessory protein Vpu modulates this incompatibility. The infectivity of HIV-1 pseudotyped with murine leukemia virus (MLV) Env was not affected by Vpu. However, the infectivity of HIV-1 pseudotyped with an MLV Env with the cytoplasmic tail from GaLV Env (MLV/GaLV Env) was restricted 50- to 100-fold by Vpu. A Vpu mutant containing a scrambled membrane-spanning domain, Vpu(RD), was still able to restrict MLV/GaLV Env, but mutation of the serine residues at positions 52 and 56 completely alleviated the restriction. Loss of infectivity appeared to be caused by reduced MLV/GaLV Env incorporation into viral particles. The mechanism of this downmodulation appears to be distinct from Vpu-mediated CD4 downmodulation because Vpu-expressing cells that failed to produce infectious HIV-1 particles nonetheless continued to display robust surface MLV/GaLV Env expression. In addition, if MLV and HIV-1 were simultaneously introduced into the same cells, only the HIV-1 particle infectivity was restricted by Vpu. Collectively, these data suggest that Vpu modulates the cellular distribution of MLV/GaLV Env, preventing its recruitment to HIV-1 budding sites.
authors.affiliation: Department of Molecular Microbiology and Immunology, Christopher S. Bond Life Science Center, University of Missouri-School of Medicine, Columbia, Missouri 65211, USA.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Lucas
authors.forename: Terri D
authors.initials: TD
authors.lastname: Lyddon
authors.forename: Paula M
authors.initials: PM
authors.lastname: Cannon
authors.forename: Marc C
authors.initials: MC
authors.lastname: Johnson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017989:Leukemia Virus, Gibbon Ape / Q000235:genetics*; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism; D019065:Virus Assembly; D000086082:Viroporin Proteins
chemical_list: D015686:Gene Products, env; D054298:Human Immunodeficiency Virus Proteins; D011993:Recombinant Fusion Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins