Mycobacterium avium induces HIV upregulation through mechanisms independent of cytokine induction.
Mycobacterium avium complex (MAC) can induce upregulation of HIV. To investigate the underlying mechanisms, the effect of MAC-induced cytokines on HIV replication was first studied. Semiquantitative RT-PCR, followed by Northern blot analysis, revealed that mRNA encoding IL-6 and TNF-alpha was induced by MAC. However, production of these cytokines was undetectable and the addition of anti-cytokine antibodies to coinfected cells could only minimally block the MAC effect on HIV. Infection of U38 cells with MAC resulted in enhancement of HIV-1 LTR-CAT transcription. In addition, transient transfection of U937 cells with full-length wild-type as well as NF-kappaB-binding site-deleted mutant HIV-1 LTR-CAT constructs revealed that MAC-induced HIV-LTR CAT is NF-kappaB dependent. These findings, together with our previous work, indicate that MAC-induced cytokine expression increases the formation of NF-kappaB, which in turn enhances HIV-1 LTR-CAT transcription. However, additional factor(s) yet to be elucidated may play a more significant role in MAC-mediated HIV-upregulation.
Ghassemi
M
M
Department of Medicine, University of Illinois, Chicago 60612, USA. Ghassemi@uic.edu
Asadi
F K
FK
Andersen
B R
BR
Novak
R M
RM
D015152:Blotting, Northern; D002460:Cell Line; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006678:HIV / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D009154:Mutation; D009162:Mycobacterium avium / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D020298:U937 Cells; D015854:Up-Regulation; D014779:Virus Replication
D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D012313:RNA