BYU researchers help find cell harboring HIV

Researchers at Brigham Young University and Johns Hopkins School of Medicine have confirmed a third type of human cell "reservoir" that harbors HIV in its infectious state, eluding treatments designed to kill the virus.

Follicular dendritic cells (FDCs), located in lymphoid tissues throughout the body, trap the virus on their surface. Because the trapped virus doesn't exhibit behavior that is looked for by medications targeting HIV — replicating, mutating, etc. — it escapes the treatment's killing attention, according to Greg Burton, BYU professor of chemistry and biochemistry.

The research, funded by the National Institutes of Health and the American Foundation for AIDS Research, will appear in Journal of Virology in June.

The discovery helps explain why treatments initially thought to be curative weren't, Burton said.

"In the mid-'90s, we had the wonderful advent of very potent anti-HIV drugs, and when people were treated with these, the virus amount in the body went to below detectable levels," he said, leading some researchers to call them a "cure."

When treatment stopped, viral counts rebounded to pretreatment levels in a couple of weeks. Study of viral DNA showed it was not, as suspected, a drug-resistance problem. Rather, it appeared that there were reservoirs where the virus remained in an infectious state, unharmed by treatment.

FDCs join two previously identified reservoirs: macrophages and latently infected CD4+ T cells.

FDCs store material needed to maintain the immune system's antibodies, releasing proteins to trigger production of specific antibodies if their numbers are low.

Burton says an FDC looks like a little octopus, with fragile long arms that grab the surrounding tissue, making it very hard to break into. The researchers figured out how to sample the virus in the reservoir and learned that it not only was stored in an infectious state, but also provided a point-in-time picture of the virus in various mutations.

The various forms of the virus they found on the surface of the cells indicates that the virus doesn't mutate in the FDC, but rather it acquires new samples over the course of time.

The human samples were provided by HIV-infected subjects at Johns Hopkins. Once the researchers figured out how to "break in" and get the stored material, BYU biologist Keith Crandall built a family tree to establish a time frame for the different viral versions.

Next, BYU graduate Trever Burgon, now seeking his doctorate at Stanford School of Medicine, sequenced individual HIV genomes from the FDCs to compare with samples taken from elsewhere in the body.