Selective in vitro protection of SIVagm-induced cytolysis by ajoene, [(E)-(Z)-4,5,9-trithiadodeca-1,6,11-triene-9 oxide].
We studied the effect of synthetic ajoene on simian immunodeficiency virus (SIVagm)-mediated cell fusion and subsequent virus-induced cytolysis. Our data indicate that this compound is a strong antifusion agent with a 50% syncytium inhibitory concentration (SIC50%) value of about 2.9 microM. We suggest that ajoene interacts with the cell-specific integrin molecules and sterically hinders the association between fusion (or other co-receptors) and the CD4-gp120 complex at the cell surface of SIV-infected cells. Although ajoene was maximally effective in suppressing syncytium formation during the early period (ie, up to 6 h) of the fusion process, when the compound was recurrently added to the co-cultures, the inhibitory effect was regained and further cell death was markedly delayed. This indicates that ajoene was also effective after the initial cell-to-cell contact stage. These data suggest that ajoene may be a promising approach for the treatment of SIV/human immunodeficiency virus (HIV) infections.
Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científica, Caracas, Venezuela.
R
R
Walder
Z
Z
Kalvatchev
R
R
Apitz-Castro
D000998:Antiviral Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology / Q000821:virology; D002459:Cell Fusion; D002470:Cell Survival / Q000187:drug effects*; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015726:Giant Cells / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D010936:Plant Extracts / Q000494:pharmacology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000472:pathogenicity*; D013454:Sulfoxides; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D004220:Disulfides; D010936:Plant Extracts; D013454:Sulfoxides; C048980:ajoene