Volume 5 Supplement 1

Fourth Dominique International Conference. Maternal chronic viral infections transmitted to infants: from mechanisms to prevention and care

Open Access

A Plasmodium falciparum antigen increases HIV-1 replication in a human placenta-derived cell line

  • Ahidjo Ayouba1,
  • Cyril Badaut2,
  • Anfumbom Kfutwah3,
  • Claude Cannou1,
  • Alexandre Juillerat2,
  • Stéphane Gangnard2,
  • Charlotte Behr4,
  • Odile Mercereau-Puijalon4,
  • Graham A Bentley2,
  • Françoise Barré-Sinoussi1 and
  • Elisabeth Menu1
Retrovirology20085(Suppl 1):P9

https://doi.org/10.1186/1742-4690-5-S1-P9

Published: 9 April 2008

Background

Malaria is endemic in countries of sub-Saharan Africa where there is also a high prevalence of HIV-1 infection, with pregnant women being the population most at risk to both infections. Epidemiological data and indirect evidence have established a link between placental malaria and an increased risk for HIV-1 mother-to-child transmission (MTCT), by unknown mechanisms.

Material and methods

The placenta-derived choriocarcinoma cell line BeWo and monocyte-derived macrophages (MDM) were infected with varying doses of luciferase reporter HIV-1 pseudotyped with the vesicular stomatitis virus protein G. A recombinant DBL3γ domain, derived from a placental Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) adhesin domain (DBL3γ-732), that binds to chondroitin sulfate A (CSA) and a non-CSA-binding PfEMP1 adhesin domain, DBL1α-varO domain were used to stimulate infected cells. In some experiments, DBL3γ-732 was preincubated with the Fab fragment of a specific or an irrelevant monoclonal antibodies (mAb) that inhibits, or not, binding to CSA. TNF-α was measured in the culture supernatants and luciferase activity was quantified at different time points in cell lysates to evaluate viral replication.

Results

Addition of DBL3γ-732 to BeWo cells, led to a dose-dependent increase of HIV-1 replication of up to 400 times the control level in the absence of DBL3γ-732. This enhancement was specific since it was inhibited by Fab fragment of an anti- DBL3γ-732 monoclonal antibody but not by the Fab of an irrelevant mAb. In contrast, the addition of DBL1α-varO domain does not increase viral replication. In MDM which presents surface CSA, both DBL domains strongly inhibit viral replication. The effect of DBL3γ-732 on HIV-1 replication is most likely mediated by TNF-α as this cytokine is significantly increased by DBL3γ-732 binding to BeWo cells and MDM.

Conclusions

This study shows, for the first time, a direct link between a P. falciparum antigen and an increase of HIV-1 replication in placental cells in vitro. If this is occuring in vivo, the presence of both infections could lead to a higher risk of HIV-1 in utero transmission. These data underline the importance of efficient malaria prophylaxis and antiretroviral interventions for pregnant women in areas where HIV-1 and malaria co-circulate.

Authors’ Affiliations

(1)
Unité Régulation des Infections Rétrovirales, Institut Pasteur
(2)
Unité d'Immunologie Structurale (C.N.R.S. U.R.A 2185), Institut Pasteur
(3)
Virology laboratory, Centre Pasteur du Cameroun
(4)
Unité d'Immunologie Moléculaire des Parasites (C.N.R.S. U.R.A 2581), Institut Pasteur

Copyright

© Ayouba et al.; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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