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Clinical Mycobacterium avium-induced HIV-1 replication is mediated by matrix metalloproteinase type 9.


Keystone Symp Mol Cell Biol Opportunist Infect AIDS. 1998 Apr 2-8;:120

We have previously shown that two clinical (serotypes 1 & 4) isolates but not a nonclinical (serotype 2) M. avium isolate enhance HIV-1 replication by 5- to 50-fold in an acute, in vitro T-cell model. The M. avium-induced HIV-1 replication was not associated with cell activation or antigen presentation. However, a cocktail of neutralizing mAb against T-cell-derived cytokines blocked clinical M. avium-induced HIV-1 replication by 50%, as measured by p24 ELISA. To better understand the mechanism of M. avium-induced HIV-1 replication, we evaluated pentoxifylline, a phosphodiesterase inhibitor, and BB3103 and MMP Inhibitor I, both matrix metalloproteinase (MMP) inhibitors. Addition of either BB3103 or MMP Inhibitor I suppressed clinical M. avium isolate-induced HIV-1 replication (p24-antigen expression) by 90%-95%, whereas pentoxifylline had no effect. Clinical but not nonclinical M. avium isolates induced MMP-9 but not MMP-2 protein expression, as measured by ELISA and confirmed by zymography. MMP inhibitors did not affect mammalian cell viability or M. avium isolate growth kinetics. Preliminary work does not suggest an effect on the HIV-1 protease which implies that the MMP inhibitors are effecting cellular interactions. MMPs are important for cell migration and effect a variety of cell surface antigens including adhesion molecules. These data suggest that M. avium-induced HIV-1 replication is mediated through MMP-9.

*Collagenases/PHYSIOLOGY *HIV-1/PHYSIOLOGY *Mycobacterium avium Complex/PHYSIOLOGY *Virus Replication/PHYSIOLOGY


Information in this article was accurate in August 30, 1998. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.