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Human monocytes/macrophages (HMM) HIV-1 infection: TNFalpha production, cell activation and microbicide activity.

Le Naour R, Raoul H, Mabondzo A, Ripoll L, Barre-Sinoussi FC, Caire Y, Dormont D; International Conference on AIDS.

Int Conf AIDS. 1991 Jun 16-21; 7: 140 (abstract no. M.A.1192).

SSA, CEA, Fontenay-aux-Roses

OBJECTIVE: To determine 1) the consequence of HIV infection on the TNFalpha synthesis and regulation, 2) the relationships between HIV infection and the different activation stages of the HMM by analysing the expression of the 1-6 fructose-biphosphatase (1-6 FBPasc) gene, and 3) the capacity of the HIV infected HMM to modify the cellular microbicidal activity through MnSOD mRNA expression quantification. METHODS: Fresh human peripheral blood monocytes (PBM) were obtained from healthy HIV-1 seronegative donors. PBM were isolated using the centrifugal elutriation technique after a ficoll-hypaque gradient, and cultured by adherence to culture dishes in RPMI 1640 supplemented with 10% fetal calf serum for 7 days, and infected with HIV1/LAV1 strain (0,02 TCID50/cell). HMM culture supernatants were recovered from 2 hours to 20 days post-infection (p.i.) for a TNFalpha cytotoxicity assay. Viral production was monitored every 2 days (P25, RT activity). At the same time-point, cells were scraped, and cytoplasmic RNAs were extracted. Northern blots analysis were performed in order to determine the expression level of the TNFalpha, MnSOD and 1-6 FBPase genes using appropriated 32P-nick-translated probes. RESULTS: HIV-1 infected HMM did not produce any biologically detectable TNFalpha during the early time p.i., despite the increase of expression level of the TNFalpha gene at 2 and 4 hours p.i.. Moreover, an increase in the translation level was detected for the MnSOD and 1-6 FBPase genes 4 hours p.i.. Remarkably, in spite of cell viral infection (P25 positive, Abott EIA), little or no MnSOD and TNFalpha, mRNAs were detectable 18 days p.i., whereas a hyperexpression of the 1-6 FBPase gene is still observed at the same time. CONCLUSIONS: The concomitant hyperexpression of TNFalpha, MnSOD and 1-6 FBPase genes, within the few hours following HIV-1 infection, may support the hypothesis that HIV infection induces a stronger activation of the HMM. Moreover, the low expression level of TNFalpha and MnSOD genes 18 days p.i. may be related with the persistence of the virus in HMM during HIV infection.

Publication Types:
  • Meeting Abstracts
Keywords:
  • AIDS Vaccines
  • Acquired Immunodeficiency Syndrome
  • Animals
  • Anti-Infective Agents
  • Blotting, Northern
  • HIV
  • HIV Envelope Protein gp160
  • HIV Infections
  • HIV Long Terminal Repeat
  • HIV-1
  • Humans
  • Macrophages
  • Monocytes
  • Superoxide Dismutase
  • genetics
  • reverse transcriptase, Human immunodeficiency virus 1
  • superoxide dismutase 2
Other ID:
  • 1119291
UI: 102182755

From Meeting Abstracts




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