[Frontiers in Bioscience 1, e42-54, August 1,1996]
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CAVEAT LECTOR



MYCOPLASMAS AND HIV INFECTION: FROM EPIDEMIOLOGY TO THEIR INTERACTION WITH IMMUNE CELLS

Catherine Brenner, Olivier Neyrolles, Alain Blanchard

Institut Pasteur, Unité d'Oncologie Virale, Département SIDA et Rétrovirus, 28, rue du Dr. Roux, 75724 Paris Cedex 15, France

Received 07/05/96; Accepted 07/09/96; On-line 08/01/96

3. IN VITRO SYNERGY BETWEEN HIV AND MYCOPLASMAS CELL KILLING ACTIVITY

Interaction between mycoplasmas and HIV was first suggested by in vitro observations following the addition of antibiotics to HIV infected-cell lines. Independently, Lemaître et al. (15) and Nozaki-Renard et al. (16) observed that the cytopathic effect of HIV was considerably reduced when tetracyclines or fluoroquinolone were added to mycoplasmas contaminated- and HIV-infected CEM cells. Lo et al. (17) and Lemaître et al. (18) demonstrated synergy increased cell death between HIV and the mycoplasmas Mycoplasma fermentans, M. penetrans, M. pirum, and M. arginini. This effect was observed when mycoplasmas were added to HIV-infected cell lines including lymphocytic CEM and the promonocytic U937 and THP1. Lemaître et al. (18) described this synergy for individual cell lysis rather than syncytia formation, whereas Lo et al. (17) reported the disappearance of HIV-associated syncytia formation in the presence of M. fermentans. In contrast, Chowdhury et al. (19) found increased HIV-infected MOLT-4 syncytia formation when extracts from the mollicute Acholeplasma laidlawii were added.

The molecular mechanism of this synergy is unknown. Quantitative analysis of electron micrographs of HIV-infected MOLT-4 cells indicates that HIV and M. fermentans tend to infect same cells (p<0.001) and that they attach to the same regions of the cell surface (in 90% of cases) (20). Possibly mycoplasmas have a direct effect on HIV attachment, entry and virion release. There is also evidence that mycoplasmas enhance HIV replication: M. pneumoniae, M. genitalium, and M. fermentans cause an increase rate in the viral replication (measured by RT and P24 assay) when added to infected human peripheral blood mononuclear cells (PBMCs) (21). Similarly, Chowdhury et al. (22) showed that heat-treated A. laidlawii extracts increased the HIV replication rate (by 45-fold) in both promonocytic J22HL-60 and U937 cells, and in monoblastic U1 cells. This stimulation involved a cellular signal transduction pathway implicating protein kinase C, as demonstrated by utilizing a specific inhibitor for this enzyme.

Oxidative stress results in a transactivation of HIV-LTR (23, 24), and various mycoplasma species (M. fermentans, M. pirum, M. penetrans, and U. urealyticum) enhance the HIV-LTR-dependent gene expression (25). Consequently increased HIV replication could, at least in part, be due to the production of reactive oxygen intermediates following cell infection with mycoplasmas (26, 27).

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