Heat shock proteins: novel therapeutic tools for HIV-infection?
Heat shock proteins (Hsps), cyclophilins (Cyps) and FK binding proteins (FKBPs) form a family of intracellular chaperone molecules that facilitate protein folding and assembly. These stress proteins are selectively expressed in cells in response to a range of stimuli, including heat, lymphokine and microbial/viral infections. This review discusses the role of stress proteins in the HIV-1 viral life cycle, with regard to the development of specific Hsp-based therapeutic strategies against HIV-1 infection. Cumulative findings are cited implicating CypA, Hsp27, Hsp70 and FKBPs in host cell and viral activation, viral entry, assembly or formation of infectious virions. Biological response modifiers that show specific high-affinity interactions with Cyp, FKBPs and Hsps, including cyclosporins, FK-506 and cyclopentenone prostaglandins respectively, may block HIV-1 replication and infection, providing novel HIV-1 therapeutic strategies. Moreover, Hsp binding to viral complexes can enhance antiviral immunity, including natural killer (NK), antibody-dependent (ADCC), gamma delta T-cell and cytotoxic T-lymphocyte (CTL) activities against HIV-1 infected cells. The ability of Hsps to interact with HIV-1 viral proteins, combined with their inherent adjuvant and immunogenic properties indicates that Hsps may also serve as vehicles for antigen delivery and the design of AIDS vaccines.
Brenner
B G
BG
McGill University, Montreal, Quebec, Canada. bbrenn1@po-box.mcgill.ca
Wainberg
Z
Z
D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000818:Animals; D021983:Cyclophilins / Q000627:therapeutic use; D003524:Cyclosporins / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D006360:Heat-Shock Proteins / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008954:Models, Biological; D018832:Molecular Chaperones; D014612:Vaccines
D003524:Cyclosporins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D018832:Molecular Chaperones; D014612:Vaccines; D021983:Cyclophilins