TNF-alpha-mediated activation of HIV-1 LTR in monocytoid cells by mycobacteria

Mycobacterial infection occurs commonly in patients with acquired immune de ficiency syndrome. Incubation of monocytoid cell line U937 cells, which was cotransfected HIV-1 long terminal repeat sequence (LTR) chloramphenicol ac etyltransferase (CAT) plasmid and Tat expression plasmid, with mycobacteriu m smegmatis, Mycobacterium avium, Mycobacterium bovis BCG and Mycobacterium tuberculosis resulted in enhancement of CAT production, indicating that th ese mycobacteria could activate LTR in this cell line. The amount of CAT in the cells coexisting with M. smegmatis was higher than that infected with other mycobacteria. The amounts of CAT production in the cells coculturing with M. avium and M. bovis BCG were intermediate. M. tuberculosis slightly stimulated CAT production. The amount of tumor necrosis factor (TNF)-alpha produced by transfected U937 cells was correlated with the amount of CAT pr oduction. The interleukin (IL)-1 beta and IL-6 levels in the supernatant fr om coculturing with all species were similar. The antibody to TNF-alpha inh ibited CAT production induced by mycobacterial infections. The anti-IL-1 be ta and anti-IL-6 antibodies, however, scarcely influenced stimulation of LT R by mycobacteria. In addition, U937 cells transfected with full length LTR CAT plasmid showed increased CAT production by activation with mycobacteri a, but the cells transfected with mutant LTR CAT constructs from which the nuclear factor (NF)-KB binding site was deleted did not show activation. Th ese findings indicated that activation of Mycobacterium-induced LTR CAT is NF-KB dependent. These findings suggested that activation of HIV-1 LTR by m ycobacteria was mainly mediated by NF-KB-induced secondary release of cytok ine TNF-alpha. (C) 2001 Federation of European Microbiological Societies. P ublished by Elsevier Science BN. All rights reserved.