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Cyclosporine blocks incorporation of HIV-1 envelope glycoprotein into virions

Sokolskaja, Elena
Olivari, Silvia
Strambio-De-Castillia, Caterina
Published in Journal of Virology. 2010, vol. 84, no. 9, p. 4851-4855
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.
Keywords Anti-HIV Agents/*pharmacologyCell LineCyclosporine/*pharmacologyHIV-1/*drug effects/*physiologyHumansT-Lymphocytes/virologyVirion/*drug effectsVirus Assembly/*drug effectsEnv Gene Products, Human Immunodeficiency Virus/*antagonists & inhibitors
PMID: 20181694
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Research group Réplication virale, pathogénèse et immunité (848)
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SOKOLSKAJA, Elena et al. Cyclosporine blocks incorporation of HIV-1 envelope glycoprotein into virions. In: Journal of Virology, 2010, vol. 84, n° 9, p. 4851-4855. https://archive-ouverte.unige.ch/unige:21321

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Deposited on : 2012-05-23

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