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