Previous investigations have shown that treatment of human peripheral blood lymphocytes (PBLs) from both uninfected and HIV-infected individuals with Brucella abortus (BA) and interleukin-2 (IL-2) results in the production of interferon-gamma (IFNg) in a synergistic fashion. IFNg is a pleiotropic lymphokine that has important immunomodulatory and antiviral activities; therefore, agents that induce the production of IFNg may be of value for inclusion in the development of human vaccines for some viral diseases. BA, or the lipopolysaccharide component of BA (BA-LPS), has been shown to induce IFNg and interacts synergistically with IL-2 to produce enhanced amounts of IFNg. Because BA or its LPS component has potential for use as a carrier in the development of a human vaccine, we are investigating the ability of BA to influence viral replication in a human cell line (H9) permissive for HIV-1 infection. A cell line is being used because previous work has shown that freshly isolated human PBLs are resistant to HIV infection and do not provide a suitable model for study. Initial experiments have shown that H9 cells show evidence of HIV-1 replication within seven days of infection. BA or BA-LPS will be added to H9 cell cultures infected with HIV-1 and cultured for seven days. Supernatants of these cultures will be assayed for p24 as an index of viral replication. IL-2 will be added to some of these cultures to determine whether or not there is any synergistic activity between BA and IL-2 in enhancing viral replication. Our previous work has shown that BA, or the combination of BA and IL-2, is capable of eliciting IFNg from the PBLs of HIV-infected individuals at different stages of disease. IF BA is to be considered for use in a human vaccine, then the studies outlined here are necessary to distinguish between the IFNg-inducing properties of BA and any possible upregulatory effects of BA on viral replication.
