Study details how long-term nonprogressors control HIV

Local collaborative research has far-reaching implications for autoimmunity, chronic infection control

July 25, 2011

HIV/AIDS researchers have long known that a group of rare individuals infected with HIV—called long-term nonprogressors—are able to control the virus without antiretroviral therapy, but the specific method of how that happens wasn’t known.

A group of Seattle-based researchers, led by Seattle BioMed’s Dr. Helen Horton and including the Center’s Drs. Julie McElrath and David Koelle of the Vaccine and Infectious Disease Division, detail one way long-term nonprogressors are able to control the disease in the July 17 online edition of Nature Medicine.

Specific human leukocyte antigens (especially HLA-B27 and HLA-B57) have long been associated with control of HIV. “Until now, we have not connected how possession of these HLA alleles (an alternative form of a gene) leads to control of the virus,” said Horton, who added that about 3 percent of the general population has HLA-B27 and HLA-B57, while an estimated 60 percent to 70 percent of long-term nonprogressors in the study possessed these two HLAs.

The findings uncover a previously unknown explanation of why HLA-B27 and HLA-B57 allele groups are associated with delayed HIV progression. During chronic infections, CD8+ T-cells (often called “killer” T-cells) become exhausted, much like any organism that is overworked.

“But they don’t die. They recognize that a cell is infected but they don’t kill it,” Horton said. “These CD8+ T-cells that see HLA B27/B57 cells in long-term nonprogressors do not get exhausted—they are continuously doing their job, which helps these individuals control the disease.” This happens because these cells don’t upregulate some key inhibitory receptors, so they cannot be switched off by regulatory T-cells (which suppress activation of the immune system).

“This is a potential explanation for why long-term nonprogressors can control HIV infection,” Horton said. “But having these allele groups is a double-edged sword. Because T-cells restricted by them cannot be suppressed by regulatory T-cells, these allele groups are beneficial in chronic infection but detrimental in autoimmunity.”

Horton added that this new information leads to more questions, which will be the next focus of research. “Our next steps will be finding out what’s different,” Horton said. “For example, why don’t these cells upregulate key inhibitory receptors?”
University of Washington, Benaroya Research Institute and Polyclinic researchers also contributed to the study.