Looking for a Needle in the Haystack

amfAR supporters ‘Meet the Scientists’ and hear about the latest in HIV cure research

How do you cure a disease when there’s so little of it in the body you can’t isolate it to study it? This was the question posed to the audience at amfAR’s “Meet the Scientists” event on June 7 at HBO Studios in New York City. They had come to hear about groundbreaking technologies being deployed by two scientists at the amfAR Institute for HIV Cure Research.

Dr. Satish Pillai

Dr. Satish Pillai

“As few as one out of a million CD4 T cells (the type of white blood cell that is attacked by HIV) may harbor the virus,” said Dr. Satish Pillai, associate investigator at the Blood Systems Research Institute in San Francisco. “It’s a true needle in a haystack problem.”

These rare cells that continue to harbor the virus, despite antiretroviral therapy, make up the reservoir that constitutes the major barrier to a cure for HIV. Despite containing HIV in their DNA, these cells remain dormant and do not appear any different from uninfected cells. Finding a way to identify and specifically target these cells remains the holy grail of HIV cure research.

Dr. Nadia Roan, an assistant professor at the University of California, San Francisco, is tackling the problem using a technology called CyTOF. She and her team stimulate cells taken from the blood or tissues to coax the virus out of hiding.

Once they have revealed which cells were infected, she explained, “We employ a form of ‘facial recognition’ technology to compare them to other cells in the body.”

Dr. Nadia Roan

Dr. Nadia Roan

The cells are characterized using up to 38 identifying markers—analogous to eye color, nose shape, etc.—and the information is used to deduce which characteristics are most likely to describe the cells that contain latent HIV. 

“We would then need to figure out how to target these cells while leaving the healthy cells alone,” Roan continued. “For example, if we find there was some protein that was only present on those cells, and not regular cells, we could target some toxin to that protein to try to eliminate those cells that way.”

Pillai is using a different set of technologies aimed at addressing the same question: Can we identify latently infected cells?

One characteristic necessarily shared by all reservoir cells is the presence of the viral genome inside the human DNA of the cell. Pillai wants to identify these cells and perform an analysis called transcriptomics, which would allow him to identify activities these cells are undergoing that might result in the production of proteins.

“We want to figure out how we can trap single cells, identify what kind of cell they are, look at surface proteins, and crack them open to see the genes inside them,” he explained.

Dr. Rowena Johnston

Dr. Rowena Johnston

Once he has identified promising patterns of gene activities or proteins, he could employ the blockbuster CRISPR technology—a relatively new breakthrough technique that allows scientists to easily edit genes with unprecedented precision—to determine the relative importance of each of the candidate gene activities or proteins in identifying reservoir cells.

CRISPR also has the potential to be used in gene therapy to cure HIV.

“CRISPR is the most exciting new development in molecular biology,” Pillai said. “It’s an elegant and simple technique for overwriting genetic mutations that underlie disease and could have a major impact on HIV.”

The ability to identify reservoir cells is central to efforts to find a cure for HIV, said amfAR Vice President and Director of Research Dr. Rowena Johnston, who moderated the discussion.

“Whichever approach produces a cure for HIV, we won’t rest until we get the job done,” she said.

amfAR thanks HBO and Moët Hennessy for their support of this event.