title: Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication by transcriptional activation at the long terminal repeat.
abstract: Tuberculosis has emerged as an epidemic fueled by the large number of individuals infected with the human immunodeficiency virus, especially those who are injecting drug users. We found a striking increase from 4- to 208-fold in p24 levels in bronchoalveolar lavage fluid from involved sites of Mycobacterium tuberculosis infection vs uninvolved sites in three HIV+ patients. We used an in vitro cell culture model to determine if tuberculosis could activate replication of HIV-1. Mononuclear phagocyte cell lines U937 and THP-1 infected with HIV-1JR-CSF, in vitro and stimulated with live M. tuberculosis H37Ra, had a threefold increase in p24 in culture supernatants. Using the HIV-1 long terminal repeat with a chloramphenicol acetyltransferase (CAT) reporter construct, live M. tuberculosis increased transcription 20-fold in THP-1 cells, and cell wall components stimulated CAT expression to a lesser extent. The nuclear factor-kappa B enhancer element was responsible for the majority of the increased CAT activity although two upstream nuclear factor-IL6 sites may also contribute to enhanced transcription. Antibodies to TNF-alpha and IL-1 inhibited the increase in CAT activity of the HIV-1 long terminal repeat by M. tuberculosis from 21-fold to 8-fold. Stimulation of HIV-1 replication by M. tuberculosis may exacerbate dysfunction of the host immune response in dually infected individuals.
authors.affiliation: Department of Medicine, New York University Medical Center, New York 10016, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Nakata
authors.forename: M
authors.initials: M
authors.lastname: Weiden
authors.forename: W N
authors.initials: WN
authors.lastname: Rom
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000821:virology; D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000032:analysis / Q000096:biosynthesis; D016325:HIV Long Terminal Repeat; D006679:HIV Seropositivity / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014376:Tuberculosis / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014779:Virus Replication
chemical_list: D000906:Antibodies; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D016655:HIV Core Protein p24; D007375:Interleukin-1; D016328:NF-kappa B; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D015500:Chloramphenicol O-Acetyltransferase