In people with HIV, killer T cells (CD8+ T cells) lack a protein called CD73, which is necessary for migration and cell movement into the tissue.
Research by University of Alberta investigators may have found the reason HIV is so good at hiding from immune system and persisting in people’s bodies.
Led by immunologist Shokrollah Elahi, Ph.D., the findings may answer a long-asked question.
They were published in PLOS Pathogens.
Elahi and his colleagues researchers discovered that in patients with HIV, killer T cells (CD8+ T cells) have very little to none of a protein called CD73, which is necessary for migration and cell movement into the tissue. Without CD73, killer T cells cannot find and eliminate HIV-infected cells.
“This mechanism explains one potential reason for why HIV stays in human tissues forever,” Elahi said in a press release. “This provides us the opportunity to come up with potential new treatments that would help killer T cells migrate better to gain access to the infected cells in different tissues.”
The research team found that chronic inflammation results in increased levels of microRNAs, a type of RNA that can bind to messenger RNAs to block them from making CD73 protein.
“We found this was causing the CD73 gene to be suppressed,” Elahi said in the press release.
The team noted that killer T cells play an important role against chronic viral infections, though their functional properties get compromised during the course of HIV infection.
CD73, is one of molecules that influences T cell functions, yet its role in the context of viral infections has never been well defined. With that in mind, the team analyzed the expression of CD73 on T cells in a cohort of 102 HIV-infected individuals. The group included those on antiretroviral therapy, those hadn’t been treated and long-term nonprogressors who were not on ART.
“We found that the frequency of T cells expressing this molecule was markedly lower among different T cell subsets obtained from the blood of HIV-infected individuals,” Elahi said. “Notably, CD73 was decreased at the intracellular protein and gene levels.”
Furthermore, the researchers discovered that T cells expressing this molecule had impaired functional properties and elevated levels of homing receptors, which suggests a migratory advantage for these cells.
By revealing why HIV remains in human tissue even after antiretroviral therapy, the three-year project could open the door to new treatments that improve the immune system’s ability to eliminate not HIV. A byproduct may be a better understanding of multiple sclerosis and insight into why people with HIV have a lower risk of developing multiple sclerosis (MS)
“Our findings suggest that reduced or eliminated CD73 can be beneficial in HIV-infected individuals to protect them against MS; therefore, targeting CD73 could be a novel potential therapeutic marker for MS patients,” Elahi said. “Moreover, we found that the elevated level of ATP in the plasma of HIV-infected individuals is responsible for the upregulation of miRNA30b, 30c and 30e, resulting in reduced expression of CD73.”