title: Cellular restriction targeting viral capsids perturbs human immunodeficiency virus type 1 infection of nondividing cells.
abstract: The ability of human immunodeficiency virus (HIV) to infect nondividing cells is a fundamental property by which HIV replicates in critical target cells, such as macrophages and resting CD4(+) T cells. Recent studies have revealed that the capsid (CA) protein is a dominant factor that determines retrovirus infectivity in nondividing cells, and several mutations in HIV type 1 (HIV-1) CA abrogate the ability of HIV-1 to infect nondividing cells. We present evidence for a connection between cellular restriction against viral capsids and the resistance of nondividing cells to retrovirus infection. TRIM proteins that are able to target incoming viral capsids restrict HIV-1 more potently in nondividing cells than in dividing cells, thus rendering HIV-1 infection dependent on cell division. Moreover, cyclophilin A, another cellular protein that binds to HIV-1 CA, regulates HIV-1 infection of nondividing cells. Together, these data demonstrate the importance of capsid-binding cellular proteins in the control of the cell cycle independence of HIV-1. We propose that cellular restrictions to retroviral infections are themselves cell cycle dependent.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamashita
authors.forename: Michael
authors.initials: M
authors.lastname: Emerman
mesh_terms: D000818:Animals; D016645:Aotidae; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002213:Capsid / Q000737:chemistry*; D002453:Cell Cycle; D002460:Cell Line; D021984:Cyclophilin A / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: D049452:Green Fluorescent Proteins; D021984:Cyclophilin A