DO BETA-CHEMOKINES HAVE CLINICAL RELEVANCE IN HIV-INFECTION

The role of beta-chemokines in HIV infection was evaluated. The kineti cs of regulated upon activation of normal T cell expressed and secrete d, macrophage inflammatory protein-1 alpha, and macrophage inflammator y protein 1 beta production by stimulated T lymphocytes did not differ substantially between HIV-infected (asymptomatic and with AIDS) and u ninfected subjects. Maximal production of these beta-chemokines by act ivated peripheral blood cells was higher in the infected individuals t han in uninfected individuals, but no significant difference was obser ved between healthy infected subjects and AIDS patients. Evaluation of the effect of HIV replication on beta-chemokine production indicated that acute infection of CD4(+) T cells with non-syncytia-inducing (NSI ) viruses generally increased beta-chemokine production two to eightfo ld, whereas with SI strains, it led to decreased production. The sensi tivity of an individual's virus to beta-chemokine-mediated inhibition correlated with the NSI virus phenotype and a healthy clinical state. 50% of the AIDS patients, however, had NSI viruses that were sensitive to beta-chemokines. Finally, anti-beta-chemokine-neutralizing antibod ies caused a more rapid release of HIV by CD4+ T cells naturally infec ted by NSI, but not SI, viruses indicating that endogenously produced chemokines can affect HIV production in culture. These findings sugges t that beta-chemokines may affect HIV replication when an NSI virus is involved, but provide little evidence that they substantially influen ce HIV infection and pathogenesis.