title: Cyclosporine blocks incorporation of HIV-1 envelope glycoprotein into virions.
abstract: Cyclosporine (CsA) decreases HIV-1 infectivity by blocking HIV-1 capsid (CA) interaction with target cell cyclophilin A (CypA). Yet, HIV-1 virions produced in the presence of CsA also exhibit decreased infectivity that was previously shown to be independent of the well-characterized HIV-1 CA-CypA interaction. Here, we demonstrate that CsA decreases gp120 and gp41 incorporation into HIV-1 virions and that the fusion of these virions with susceptible target cells is impaired. This effect was not observed with HIV-1 virions pseudotyped with the vesicular stomatitis virus glycoprotein or with the amphotropic envelope protein of murine leukemia virus. It was independent of calcineurin signaling, the endoplasmic reticulum luminal protein cyclophilin B, and the long cytoplasmic tail of gp41. Thus, cyclosporine blocks HIV-1 infectivity via two independent mechanisms, the first involving HIV-1 CA in target cells and the second involving HIV-1 Env in producer cells.
authors.affiliation: Department of Microbiology, Columbia University, New York, New York 10032, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Sokolskaja
authors.forename: Silvia
authors.initials: S
authors.lastname: Olivari
authors.forename: Madeleine
authors.initials: M
authors.lastname: Zufferey
authors.forename: Caterina
authors.initials: C
authors.lastname: Strambio-De-Castillia
authors.forename: Massimo
authors.initials: M
authors.lastname: Pizzato
authors.forename: Jeremy
authors.initials: J
authors.lastname: Luban
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D013601:T-Lymphocytes / Q000821:virology; D014771:Virion / Q000187:drug effects*; D019065:Virus Assembly / Q000187:drug effects*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors*
chemical_list: D019380:Anti-HIV Agents; D054299:env Gene Products, Human Immunodeficiency Virus; D016572:Cyclosporine