4712500_monash_163872.pdf (14.14 MB)
Dendritic cell regulation of HIV-1 latency in CD4+ T-cell
thesisposted on 2017-03-02, 03:54 authored by Kumar, Nitasha Asmita
Combination antiretroviral therapy (cART) is able to control HIV-1 replication and prevent acquired immune deficiency syndrome (AIDS), however does not provide a cure. The major barrier to HIV-1 cure is the persistence of long-lived, latently infected resting CD4+ T-cells. We developed an in vitro dendritic cell (DC)-T-cell latency model, which showed that myeloid (m)DC induced post-integration latent infection in non-proliferating, resting and proliferating CD4+ T-cells. Gene expression profiles indicated that mDC could regulate the establishment of latent infection in non-proliferating and proliferating CD4+ T-cells through interaction between adhesion molecules, co-stimulatory molecules and immune checkpoints. On the contrary, pDC-T-cell interactions led to the inhibition of latent infection in co-cultured resting CD4+ T-cells and death of proliferated CD4+ T-cells. Gene expression profiles suggested that inhibition is mediated through type-I and III interferons. Investigation of the mechanisms of mDC mediated establishment of latent infection and pDC mediated inhibition of latent infection, may provide novel elimination strategies for HIV-1 cure.