Inhibition of HIV-1, HIV-2 and SIV envelope glycoprotein-mediated cell fusion by calmodulin.
Calmodulin, an EF-hand protein, inhibited the fusion between CD4+ human cells and cells stably expressing HIV-1 envelope proteins. Fusion was also inhibited when HIV-1, HIV-2 or SIV envelope glycoproteins were expressed by vaccinia virus (VV) recombinants, but calmodulin did not inhibit syncytia formation induced by measles virus glycoproteins. Calmodulin also inhibited fusion induced by vPE17, a VV-recombinant expressing a truncated form of HIV-1gp160 which lacks the two known calmodulin-binding sites located in the cytoplasmic domain of gp41. The inhibitory activity was specific to calmodulin among the EF-hand proteins. These observations may be important in understanding the mechanism of retroviral envelope glycoprotein-mediated cell fusion. Several possible mechanisms of action are discussed.
Malvoisin
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Inserm Unit 404, Immunity and Vaccination, Institut Pasteur de Lyon, France. fwipaly@imaginet.fr
Wild
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D019380:Anti-HIV Agents / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D002459:Cell Fusion / Q000187:drug effects; D002460:Cell Line; D015686:Gene Products, env / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015700:HIV Envelope Protein gp41 / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D017958:Lentiviruses, Primate / Q000187:drug effects* / Q000502:physiology; D008459:Measles virus / Q000187:drug effects / Q000502:physiology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000502:physiology
D019380:Anti-HIV Agents; D002147:Calmodulin; D015686:Gene Products, env; D015700:HIV Envelope Protein gp41