Involvement of matrix metalloproteinases in human immunodeficiency virus type 1-induced replication by clinical Mycobacterium avium isolates.
The role of Mycobacterium avium isolates in modulating human immunodeficiency virus type 1 (HIV-1) replication was examined by use of an in vitro, resting T cell system. Two human clinical isolates (serotypes 1 and 4) but not an environmental M. avium isolate (serotype 2) enhanced HIV-1 replication. The M. avium-induced HIV-1 replication was not associated with cell activation or differential cytokine production or utilization. Addition of matrix metalloproteinase (MMP) inhibitors and their in vivo regulators, tissue inhibitors of metalloproteinases-1 and -2, abrogated M. avium-induced HIV-1 replication 80%-95%. The MMP inhibitors did not have any effect on the HIV-1 protease activity, suggesting that they may affect cellular processes. Furthermore, MMP-9 protein was differentially expressed after infection with clinical M. avium isolates and paralleled HIV-1 p24 production. Collectively, these data suggest that M. avium-induced HIV-1 replication is mediated, in part, through the induction of MMP-9.
Dezzutti
C S
CS
HIV and Retrovirus Diseases Branch, Centers for Disease control and Prevention, Atlanta, Georgia, USA. cyd5@cdc.gov
Swords
W E
WE
Guenthner
P C
PC
Sasso
D R
DR
Wahl
L M
LM
Drummond
A H
AH
Newman
G W
GW
King
C H
CH
Quinn
F D
FD
Lal
R B
RB
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D016333:HIV Protease / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000821:virology*; D008264:Macrophages / Q000201:enzymology / Q000382:microbiology / Q000821:virology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D015269:Mycobacterium avium Complex / Q000145:classification / Q000302:isolation & purification / Q000502:physiology*; D015270:Mycobacterium avium-intracellulare Infection / Q000382:microbiology; D010431:Pentoxifylline / Q000494:pharmacology; D012703:Serotyping; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000494:pharmacology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology*; D014376:Tuberculosis / Q000382:microbiology / Q000662:veterinary; D014779:Virus Replication / Q000187:drug effects
D016655:HIV Core Protein p24; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D016333:HIV Protease; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9; D010431:Pentoxifylline