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Generation of an In Vitro Cell Culture Model of Malaria-HIV Co-Infection

Generation of an In Vitro Cell Culture Model of Malaria-HIV Co-Infection

Transcription

Begin with a multi-well plate containing human peripheral blood mononuclear cells, or PBMCs derived from a human immunodeficiency virus, or HIV-infected donor.

PBMCs contain various immune cells, including HIV-infected CD4-positive T cells with integrated proviral DNA.

Seed the wells with a mixture of Plasmodium falciparum parasitized erythrocytes, or PfRBCs — expressing parasite-derived antigens, and uninfected RBCs.

During incubation, the PfRBCs' antigens interact with receptors of immune cells, activating them and releasing cytokines.

These cytokines trigger downstream signaling in CD4 T cells, initiating transcription of HIV proviral DNA and synthesis of new viral RNAs.

The viral RNAs and HIV proteins form virus particles that bud off, infecting new CD4 T cells and spreading HIV infection.

Progressive HIV infection disrupts cytokine secretion, impairing the immune response against PfRBCs and leading to persistent malaria infection.

Over time, infected RBCs release parasites that invade new RBCs, proliferating malarial parasites and establishing the malaria-HIV co-infection cell culture model.

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