HIV Controllers Exhibit Specialized Antiviral Capacities

OLIVIA ANGIULI ’15

Olivia Angiuli Image, VIA Assay.jpg

I have been comparing how effectively HIV-infected CD4+ T cells are killed by CD8+ T cells isolated from elite controllers, chronic progressors, and HIV negative patients.

Human Immunodeficiency Virus (HIV) is a virus that replicates by hijacking the host machinery of key cells in the human immune system, focusing mainly on CD4+ T cells, a type of white blood cell that helps regulate immune response. Curiously, less than 1% of people who become infected with HIV (a group known as “elite controllers”) can maintain undetectable levels of the virus in their plasma, the nutrient-carrying part of blood, whereas most untreated HIV-infected patients, “chronic progressors,” show active viral replication with thousands of viral copies per milliliter of plasma.

Under the supervision of Dr. David Shasha, I have been examining how effectively HIV-infected CD4+ T cells are killed by CD8+ T cells. Isolated from elite controllers, chronic progressors, and HIV-negative patients, these CD8+ T cells are responsible for destroying virally infected and tumorous cells in the body. We use viral inhibition assays (VIAs), a type of test in which CD8+ T cells are mixed with HIV-infected CD4+ T cells, to test whether CD8+ T cells have the ability to kill HIV-infected cells.

Previous studies have demonstrated that CD8+ T cells of elite controllers show stronger inhibition of the HIV virus than CD8+ T cells from chronic progressors. Our preliminary results suggest that this difference in the two populations of CD8+ T cells is only present when CD8+ T cells rest for three days without any exposure to the virus. CD8+ T cells from chronic progressors that do not undergo a three-day rest period may in fact exhibit equal abilities to kill HIV-infected cells as those of elite controllers. This may suggest that elite controllers’ CD8+ T cells are not necessarily more effective at killing HIV-infected cells, but merely survive longer or exhibit better functionality after prolonged incubation in vitro.  The next step in this line of research might be to regulate chronic progressors’ white blood cells so that they also are able to function well after a three-day rest period.  This “cure” for HIV would not focus on treatment itself; rather, it would be a simple measure to increase our immunity to this disease.

The writer can be reached at oangiuli@college.harvard.edu.