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Dendritic cell regulation of HIV-1 latency in CD4+ T-cell

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thesis
posted on 02.03.2017, 03:54 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.

History

Principal supervisor

Sharon R Lewin

Additional supervisor 1

Paul U Cameron

Additional supervisor 2

Vanessa A Evans

Year of Award

2016

Department, School or Centre

Infectious Disease

Campus location

Australia

Degree Type

DOCTORATE

Faculty

Faculty of Medicine Nursing and Health Sciences