11th International AIDS Conference Vancouver, British Columbia — July 7-12, 1996

Int Conf AIDS 1996 Jul 7-12; 11:22 (abstract no. LB.A.6003)
Zybarth G, Dubrovsky L, Bucala R, Ulrich P, Rich D, Cerami A, Sherry B, Bukrinsky M; The Picower Institute for Medical Research, Manhasset, NY. Fax: (516) 365-5090.

OBJECTIVE: To determine whether viral-associated cyclophilin facilitates HIV-1 entry or uncoating by interacting with a putative cyclophilin binding protein accessible on the surface of target cells.

METHODS: PBMCs and cell lines were infected with HIV-1 in the presence and absence of excess exogenously added cyclophilin and inhibitors.

RESULTS: Firstly, recombinant cyclophilin added together with infecting virus inhibits HIV-1 infection in a dose-dependent manner. Inhibition was observed in both primary T lymphocyte and monocyte cultures, as well as in CD4+ T cell lines. PCR analysis demonstrated that excess exogenously added cyclophilin affected either the early step of reverse transcription or events prior to it. Secondly, neutralizing antibodies raised against cyclophilin suppressed HIV-1 infection. Finally, a non-immunosuppressive cyclosporin A analog modified by the attachment of a bulky side group that prevents uptake of this drug by T cells inhibited HIV-1 infection in the same manner as excess cyclophilin.

CONCLUSIONS: These results are compatible with the hypothesis that cyclophilin is exposed, at least in part, on the virion surface at some point during the infection process and functions as a ligand that facilitates viral entry into cells or proper targeting of virus to a subcellular compartment required for efficient uncoating, reverse transcription, and pre-integration complex formation. These findings suggest novel approaches for the design of anti-HIV drugs and vaccines.

960707
LBA6003

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