HIV inactivation by cross-linking of photo-labeled anti-retroviral compounds with HIV reverse transcriptase.
We describe a new method for the development of a preventive inactivated-HIV vaccine, based on photo-inactivation of HIV reverse transcriptase (RT), which preserves both the conformational and functional integrity of viral surface proteins. The RT of HIV-1 was selectively targeted for inactivation using a photo-labeled compound with specific affinity for HIV-1 RT. The photo-labeled virions were then exposed to UV light causing the photo-labeled compound to form a covalent bond cross-linking the photo-active compound to RT. Replication capacity of the treated virions was significantly reduced when compared to controls suggesting that exposure of treated virions to UV light had caused a stable interaction of RT and the photo-labeling compound.
Colby-Germinario
Susan
S
McGill AIDS Center, Lady Davis Institute, Jewish General Hospital, 3755 Côte Ste. Catherine, Montréal, Canada H3T-1E2.
Rios
Adan
A
Quesada
Jorge
J
Anderson
Dallas
D
Goldstein
Allan L
AL
Fossum
Theresa
T
Wainberg
Mark A
MA
D016915:AIDS Vaccines / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003432:Cross-Linking Reagents; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections; D054303:HIV Reverse Transcriptase / Q000528:radiation effects*; D015497:HIV-1 / Q000528:radiation effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D019920:Photoaffinity Labels; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*; D013379:Substrate Specificity; D014466:Ultraviolet Rays; D038301:Virus Inactivation
D016915:AIDS Vaccines; D003432:Cross-Linking Reagents; D016655:HIV Core Protein p24; D019920:Photoaffinity Labels; D018894:Reverse Transcriptase Inhibitors; C514799:p24 protein, Human Immunodeficiency Virus Type 1; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase