P. falciparum Enhances HIV Replication in an Experimental Malaria Challenge System

Marika Orlov,Florin Vaida,Olivia C Finney,Qianqian Deng,Ruobing Wang,Stefan H Kappe,Patrick E Duffy,Angela K Talley,Robert T Schooley,David M Smith,James G Beeson

doi:10.1371/journal.pone.0039000

Marika Orlov, Florin Vaida + Show 9 more

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https://doi.org/10.1371/journal.pone.0039000

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Journal: PloS one	Publication Date: Jun 26, 2012
Citations: 17	License type: CC0 1.0

Affiliation: University of California, San Diego

Abstract

Co-infection with HIV and P. falciparum worsens the prognosis of both infections; however, the mechanisms driving this adverse interaction are not fully delineated. To evaluate this, we studied HIV-1 and P. falciparum interactions in vitro using peripheral blood mononuclear cells (PBMCs) from human malaria naïve volunteers experimentally infected with P. falciparum in a malaria challenge trial.PBMCs collected before the malaria challenge and at several time points post-infection were infected with HIV-1 and co-cultured with either P. falciparum infected (iRBCs) or uninfected (uRBCs) red blood cells. HIV p24Ag and TNF-α, IFN-γ, IL-4, IL-6, IL-10, IL-17, and MIP-1α were quantified in the co-culture supernatants. In general, iRBCs stimulated more HIV p24Ag production by PBMCs than did uRBCs. HIV p24Ag production by PBMCs in the presence of iRBCs (but not uRBCs) further increased during convalescence (days 35, 56, and 90 post-challenge). In parallel, iRBCs induced higher secretion of pro-inflammatory cytokines (TNF-α, IFN-γ, and MIP-1α) than uRBCs, and production increased further during convalescence. Because the increase in p24Ag production occurred after parasitemia and generalized immune activation had resolved, our results suggest that enhanced HIV production is related to the development of anti-malaria immunity and may be mediated by pro-inflammatory cytokines.

Highlights

HIV-1 and Plasmodium falciparum malaria remain two of SubSaharan Africa’s major causes of morbidity and mortality
Whole peripheral blood mononuclear cells (PBMCs) isolated from HIV uninfected, malaria naıve donors produced significantly more HIV when co-cultured with infected Red Blood Cells (iRBCs) than when co-cultured with uRBCs (Figure 1B inset, p = 0.0045, area under the curve comparisons)
For all of the participants at the baseline, liver stage, and blood stage visits, the amount of HIV produced from the PBMCs co-cultured with iRBCs was about 2 fold higher than the amount of HIV produced from the PBMCs co-cultured with uRBCs

Summary

Introduction

HIV-1 and Plasmodium falciparum malaria remain two of SubSaharan Africa’s major causes of morbidity and mortality. A mathematical model further explored the potential importance of the malaria/ HIV interaction Based on this model, in an area of Kenya, with an adult population of roughly 200,000 that has been exposed to both pathogens since 1980, the interaction of the two diseases may have caused 8,500 excess HIV infections and 980,000 excess malaria episodes [8]. In an area of Kenya, with an adult population of roughly 200,000 that has been exposed to both pathogens since 1980, the interaction of the two diseases may have caused 8,500 excess HIV infections and 980,000 excess malaria episodes [8] Supporting this mathematical model, a study that examined geographical overlap of the two pathogens in East Africa found that those who live in areas of high P. falciparum incidence have about twice the risk of being HIV infected compared to individuals who live in areas of low incidence [9]

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