Spontaneous production of C-C chemokines by individuals infected with human T lymphotropic virus type II (HTLV-II) alone and HTLV-II/HIV-1 coinfectedindividuals

To investigate the immunological features of human T lymphotropic virus typ e II (HTLV-II) infection and specific mechanisms whereby HTLV-II might infl uence the progression of HIV-1 disease in coinfected individuals, we have a nalyzed the production of the C-C chemokines RANTES and macrophage inflamma tory proteins 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta) by PBMCs from HTLV-II-infected and HTLV-II/HIV-1-coinfected individuals. We observed spo ntaneous production of significant levels of MIP-1 alpha and -1 beta and, t o a lesser extent, RANTES, from individuals infected with HTLV-II alone or with concomitant HIV-1 infection. Spontaneous C-C chemokine production was not observed in PBMCs' from uninfected or HIV-1-infected individuals. Altho ugh HTLV-II is known to preferentially infect CD8(+) lymphocytes in vivo, w e observed that whereas RANTES was produced exclusively by the CD8(+)-enric hed fraction, MIP-1 alpha and -1 beta were produced by both the CD8(+)-enri ched and CD8(+)-depleted fractions of HTLV-II-infected PBMCs, RT-PCR demons trated active expression of the HTLV-II regulatory protein Tax in the infec ted CD8(+) T lymphocyte population, and it wag further shown that Tax trans activates the promoters of MIP-1 beta and RANTES, Therefore, it appears tha t HTLV-II stimulates the production of C-C chemokines both directly at a tr anscriptional level via the viral transactivator Tax and also indirectly. A lthough the HTLV-II-infected individuals in this study are all virtually as ymptomatic, they certainly display an abnormal immune phenotype. Moreover, our findings suggest that HTLV-II, via chemokine production, would be expec ted to alter the progression of HIV-1 infection in coinfected individuals.