title: The cellular protein lyric interacts with HIV-1 Gag.
abstract: Human immunodeficiency virus type 1 (HIV-1) Gag is the main structural protein driving assembly and release of virions from infected cells. Gag alone is capable of self-assembly in vitro, but host factors have been shown to play a role in efficient viral replication and particle morphogenesis within the living cell. In a series of affinity purification experiments, we identified the cellular protein Lyric to be an HIV-1 Gag-interacting protein. Lyric was previously described to be an HIV-inducible gene and is involved in various signaling pathways. Gag interacts with endogenous Lyric via its matrix (MA) and nucleocapsid (NC) domains. This interaction requires Gag multimerization and Lyric amino acids 101 to 289. Endogenous Lyric is incorporated into HIV-1 virions and is cleaved by the viral protease. Gag-Lyric interaction was also observed for murine leukemia virus and equine infectious anemia virus, suggesting that it represents a conserved feature among retroviruses. Expression of the Gag binding domain of Lyric increased Gag expression levels and viral infectivity, whereas expression of a Lyric mutant lacking the Gag binding site resulted in lower Gag expression and decreased viral infectivity. The results of the current study identify Lyric to be a cellular interaction partner of HIV-1 Gag and hint at a potential role in regulating infectivity. Further experiments are needed to elucidate the precise role of this interaction.
authors.affiliation: Department of Infectious Diseases, Virology, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Engeland
authors.forename: Heike
authors.initials: H
authors.lastname: Oberwinkler
authors.forename: Michael
authors.initials: M
authors.lastname: Schümann
authors.forename: Eberhard
authors.initials: E
authors.lastname: Krause
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Müller
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kräusslich
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015497:HIV-1 / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D004860:Infectious Anemia Virus, Equine / Q000472:pathogenicity; D009052:Leukemia Virus, Murine / Q000472:pathogenicity; D008565:Membrane Proteins; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus