title: Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells.
abstract: The post-entry events of HIV-1 infection occur within reverse transcription complexes derived from the viral cores entering the target cell. HIV-1 cores contain host proteins incorporated from virus-producing cells. In this report, we show that MCM5, a subunit of the hexameric minichromosome maintenance (MCM) DNA helicase complex, associates with Gag polyprotein and is incorporated into HIV-1 virions. The progeny virions depleted of MCM5 demonstrated reduced reverse transcription in newly infected cells, but integration and subsequent replication steps were not affected. Interestingly, increased packaging of MCM5 into the virions also led to reduced reverse transcription, but here viral replication was impaired. Our data suggest that incorporation of physiological amounts of MCM5 promotes aberrant reverse transcription, leading to partial incapacitation of cDNA, whereas increased MCM5 abundance leads to reduced reverse transcription and infection. Therefore, MCM5 has the properties of an inhibitory factor that interferes with production of an integration-competent cDNA product.
authors.affiliation: George Washington University School of Medicine and Health Sciences, Department of Microbiology, Immunology and Tropical Medicine, 2300 I Street NW, Ross Hall, Washington, DC 20037, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Santos
authors.affiliation: Howard University College of Medicine, Department of Medicine, Center for Sickle Cell Disease, 1840 7th Street N.W., Washington DC 20001, USA; Howard University College of Medicine, RCMI Proteomics Core Facility, 1840 7th Street N.W., Washington DC 20001, USA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Obukhov
authors.affiliation: Howard University College of Medicine, Department of Medicine, Center for Sickle Cell Disease, 1840 7th Street N.W., Washington DC 20001, USA; Howard University College of Medicine, RCMI Proteomics Core Facility, 1840 7th Street N.W., Washington DC 20001, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Nekhai
authors.affiliation: George Washington University School of Medicine and Health Sciences, Department of Microbiology, Immunology and Tropical Medicine, 2300 I Street NW, Ross Hall, Washington, DC 20037, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Pushkarsky
authors.affiliation: George Washington University School of Medicine and Health Sciences, Department of Microbiology, Immunology and Tropical Medicine, 2300 I Street NW, Ross Hall, Washington, DC 20037, USA.
authors.forename: Beda
authors.initials: B
authors.lastname: Brichacek
authors.affiliation: George Washington University School of Medicine and Health Sciences, Department of Microbiology, Immunology and Tropical Medicine, 2300 I Street NW, Ross Hall, Washington, DC 20037, USA. Electronic address: mbukrins@gwu.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Bukrinsky
authors.affiliation: George Washington University School of Medicine and Health Sciences, Department of Microbiology, Immunology and Tropical Medicine, 2300 I Street NW, Ross Hall, Washington, DC 20037, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Iordanskiy
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D014771:Virion; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C489423:MCM5 protein, human; D046912:Multiprotein Complexes; D054301:gag Gene Products, Human Immunodeficiency Virus
keywords: DNA helicase; HIV-1; Integration; MCM5; Minichromosome maintenance complex; Reverse transcription; Viral replication