Clastogenic factors in plasma of HIV-1 infected patients activate HIV-1 replication in vitro: inhibition by superoxide dismutase.
The frequent neoplastic disorders present in HIV-infected patients and the implication of oxidative stress in AIDS-Kaposi's sarcoma pathogenesis prompted us to study whether the mechanisms implicated in genotoxic effects of clastogenic factors (CFs) (i.e., chromosome damaging materials released by cells under conditions of oxidant stress) can play a role in HIV-1 expression and whether exogenous superoxide dismutase can inhibit the clastogenic and HIV-inducing effects of CFs. CFs were found in the plasma of all HIV-1 infected patients (n = 21) of this study group, in asymptomatic (CDC II) as well as in symptomatic patients (CDC IV). In addition to their chromosome damaging effect, CFs are able to upregulate HIV-1 expression in U1 cells and in PBMCs activated with PHA and IL2 at all time points (p < .05). Their formation, therefore, is an early event in the disease. It occured despite antiviral medication in these patients. Superoxide dismutase inhibited the clastogenic and the viral inducing effects (p < .05). On the basis of our findings, association of SOD mimetics or superoxide scavengers with antiviral drugs may be a new therapeutic approach. This polytherapy, if started early enough after infection, may prolong the latency period and limit the emergence of drug-resistant viral strains.
Edeas
M A
MA
Department of Biochemistry, Hôpital Antoine Béclère, Clamart, France.
Emerit
I
I
Khalfoun
Y
Y
Lazizi
Y
Y
Cernjavski
L
L
Levy
A
A
Lindenbaum
A
A
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D009153:Mutagens / Q000378:metabolism / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014779:Virus Replication
D007376:Interleukin-2; D009153:Mutagens; D010835:Phytohemagglutinins; D013482:Superoxide Dismutase