Tat protein from HIV-1 binds to Mycobacterium avium via a bacterial integrin. Effects on extracellular and intracellular growth.
We examined the interaction between HIV-1 Tat protein and the opportunistic pathogen Mycobacterium avium. AIDS-associated strains of M. avium were shown to bind Tat protein quite avidly in an attachment assay. The attachment of M. avium to Tat was shown to occur via the integrin alpha 5 beta 1 present on the mycobacterial cell surface. M. avium strains were shown to bind the viral Tat protein with high affinity in a specific fashion (600 binding sites with a Kd of 1 to 5 nM). M. avium coated with Tat protein were shown to be more infective for human alveolar macrophages than untreated M. avium. Other HIV-1 Ags had no such effects (e.g., p24, p17). Examination of the cytokine profile of infected macrophages showed that M. avium-Tat complexes induced higher levels of TGF beta-1 (TGF beta 1) than M. avium alone or M. avium that had been in contact with other viral proteins. Conditioned media from HIV-1-infected H9 cells released a factor that enhanced M. avium intramacrophage growth, and was partially neutralized by an anti-Tat Ab. Finally, Tat protein (purified or present in conditioned media from infected cells) moderately enhanced the growth of M. avium strains in extracellular media, and exposure of M. avium to Tat protein in the presence of IL-6 enhanced the growth of AIDS-associated strains. These data argue for an interaction between the Tat viral product and the opportunistic pathogen M. avium which may contribute to the exquisite susceptibility of AIDS subjects to this pathogen.
Denis
M
M
Pulmonary Research Unit, Faculty of Medicine, University of Sherbrooke, Canada.
D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology*; D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology*; D001422:Bacterial Adhesion; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D015850:Interleukin-6 / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000382:microbiology; D015846:Monokines / Q000378:metabolism; D009162:Mycobacterium avium / Q000254:growth & development* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D016023:Integrins; D015850:Interleukin-6; D015846:Monokines; D016212:Transforming Growth Factor beta; D054322:tat Gene Products, Human Immunodeficiency Virus