The role of Natural Killer cells in preventing HIV-1 acquisition and controlling disease progression

Vivek Naranbhai, Salim S Abdool Karim, William Carr

Abstract


Given the dearth and limitation of study on the role of Natural Killer cells in HIV acquisition

and control, in the studies proposed for this PhD we seek to determine whether and how

Natural Killer cells are involved in HIV-1 acquisition and control by studying NK cells using a

unique assembly of existing patient cohorts studied through the Centre for the AIDS

Programme of Research and the HIV Pathogenesis Programme. By alloying patient samples

from patients with varying levels of exposure to HIV-1 (unexposed uninfected, exposed

uninfected, and exposed pre-infected), and with varying outcomes of exposure (acutely

infected, chronically infected untreated and chronically infected treated) with the advanced

techniques we now have access to at the UKZN (including multiparametric flow cytometry

and viral culture facilities), and novel assays probing mechanisms of specific HIV-infected

target recognition and HIV replication inhibition, we will address the objectives as outlined

above. While testing hypotheses 1.1, 2.1, 2.2, 3.1 and 3.2 will form the bulk of the work for

this project, we will have unique advantage of the fact that a proportion of samples to be

used in this study are to be obtained from a Phase IIb randomized controlled clinical trial in

which woman exposed to HIV are randomized to use 1% Tenofovir gel or placebo.

Hypotheses 1.2 and 2.4 will be evaluated to test how Tenofovir, by potentially aborting

infection at the level of the mucosa or regional lymph node, may facilitate NK cell

‘recognition’ of the virus and how this may modify NK cell activity in those uninfected with HIV.