Characterization of immune suppression by a synthetic HIV gp41 peptide

HIV infection is associated with immunosuppression leading to susceptibility to opportunistic infections and tumors. HIV proteins can be immunosuppressive with substantial activity residing within the gp41 portion of HIV envelope glycoprotein gp160. In this report, immunosuppressive properties of a synthetic peptide corresponding to amino acid sequence 584-609 of HIV-1 transmembrane protein gp41 were investigated. The peptide was found to inhibit proliferative responses of normal human lymphocytes to mitogens and recall antigen. Stimulations by IL-2 and by anti-CD3 were also inhibited, indicating that the effect occurred in a pathway of response shared by CD3 and by IL-2 receptor recognition systems. Both CD4 and CD8 T cells were suppressed, indicating that the suppression did not require interactions with CD4 molecules. Consistently, the peptide was suppressive in the presence of HIV-infected patients' sera containing specific antibodies to the peptide, suggesting that the active portion was probably not an immunogenic configuration. These in vitro results emphasize the likelihood that HIV gp41 contributes to the in vivo immunosuppression and immune dysfunction of HIV-infected persons.