Heat shock protein-based therapeutic strategies against human immunodeficiency virus type 1 infection.
Heat shock proteins (hsps) and cyclophilins (CypA) are intracellular chaperone molecules that facilitate protein folding and assembly. These proteins are selectively expressed in cells following exposure to a range of stress stimuli, including viral infection. Hsp species are highly immunogenic, eliciting humoral, cytotoxic T lymphocyte (CTL), and natural killer (NK) cell responses against viruses, tumours, and infectious diseases. This review discusses the roles of stress proteins in immunity and viral life cycles, vis-à-vis the development of Hsp-based therapeutic strategies against human immunodeficiency virus type-1 (HIV-1) infection. Cumulative findings are cited implicating the requirement of CypA in HIV-1 replication and formation of infectious virions. Studies by our group show the upregulated expression of hsp27 and hsp70 during single-cycle HIV infections. These species redistribute to the cell surface following HIV-infection and heat stress, serving as targets for NK and antibody-dependent cellular cytotoxicity. Co-immunoprecipitation and Western blot studies show that hsp27, hsp70, and hsp78 complex with HIV-1 viral proteins intracellularly. Hsp70, hsp56, and CypA are assembled into HIV-1 virions. The ability of hsps to interact with HIV-1 viral proteins, combined with their inherent adjuvant and immunogenic properties, indicates that hsps may serve as vehicles for antigen delivery and the design of vaccines against acquired immunodeficiency syndrome.
Brenner
B G
BG
McGill AIDS Centre, Lady Davis Institute, Jewish General Hospital, and Department of Experimental Surgery, McGill University, Montreal, Quebec, Canada. mdbl@musica.mcgill.ca
Wainberg
M A
MA
D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D019696:Peptidylprolyl Isomerase / Q000276:immunology*; D014612:Vaccines
D006360:Heat-Shock Proteins; D014612:Vaccines; D019696:Peptidylprolyl Isomerase