PHAGOCYTOSIS OF MYCOBACTERIUM-TUBERCULOSIS MODULATES HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION IN HUMAN MONOCYTIC CELLS

Macrophage activation resulting from phagocytosis has the potential to modulate human immunodeficiency virus (HIV) replication. We have dete rmined the effects of phagocytosis of particulate stimuli on transcrip tion and release of HIV. Using THP-1 and Mono Mac 6 human monocytic ce ll lines transfected with HIV long terminal repeat sequence chloramphe nicol acetytransferase (LTR CAT) constructs we have demonstrated that phagocytosis of Mycobacterium tuberculosis enhanced HIV-1 and -2 LTR C AT expression. However phagocytosis of zymosan or inert latex beads ha d little or no effect on CAT expression. Enhancement of HIV LTR CAT ex pression was dependent upon intact NF-kappa B binding sites and was in dependent of tumour necrosis factor alpha secretion. M tuberculosis st rains of different degrees of virulence induced similar levels of enha nced CAT expression. In contrast, phagocytosis of M. tuberculosis by H IV-l-infected THP-1 cells reduced supernatant reverse transcriptase (R T) activity without suppression of p24 antigen release. Phagocytosis o f zymosan granules or latex particles did not alter released RT activi ty. However, phagocytosis of either M. tuberculosis, zymosan granules or latex particles by HIV-1-infected human peripheral blood monocyte-d erived macrophages reduced supernatant RT activity. These data indicat e that phagocytosis of M. tuberculosis may enhance HIV transcription i n monocytic cells although it may reduce release of intact HIV.