Lipids and retroviruses.
The role that lipids may play in enveloped viruses is reviewed. Small lipid molecules can influence retrovirus binding to cell receptors, plasma membrane fusion, and transcription. Palmitoylation following myristoylation of viral glycoproteins is required at the transmembrane level for signal transduction as well as for virion budding and maturation. Cholesterol, ether lipids, phospholipids, platelet-activating factor, phosphatidic acids, diacylglycerols, and several analogs and derivatives influence human immunodeficiency virus (HIV) activity; when conjugated with inhibitors of the viral reverse transcriptase (RT) or aspartyl protease these compounds increase drug effectiveness. On the other hand, L-carnitine, in association with the mitochondrial cardiolipins, inhibits myopathy due to continued prescription of drugs [AZT (zidovudine), ddl (didanoside), or ddC (zalcitabine)], and the redox couple of alpha-lipoic-dihydrolipoic acid prevents production of the reactive oxygen species that trigger apoptosis of infected cells, with sphingomyelin breakdown to ceramides. Retroviral infection induces a shift from phospholipid to neutral fat synthesis in host cells, and a long antiviral, i.e., antiprotease, treatment may lead to lipodystrophy. Multitherapy involving lipids and their analogs in association with anti-RT and antiproteases might enhance the inhibition of growth and proliferation of retroviruses.
Raulin
J
J
Université Denis Diderot (Paris 7), France. craulin@aol.com
D019380:Anti-HIV Agents / Q000494:pharmacology*; D001692:Biological Transport; D002308:Cardiolipins / Q000378:metabolism; D002331:Carnitine / Q000378:metabolism; D006678:HIV / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D011355:Prodrugs / Q000494:pharmacology; D012190:Retroviridae / Q000472:pathogenicity / Q000502:physiology*; D012192:Retroviridae Infections / Q000188:drug therapy* / Q000821:virology; D015398:Signal Transduction
D019380:Anti-HIV Agents; D002308:Cardiolipins; D008055:Lipids; D011355:Prodrugs; D002331:Carnitine