Researchers from Emory University have found an extra HIV/SIV reservoir where immune cells survive and harbor the virus. The work was published in yesterday's Immunity.
In this study, the team infected macaques with SIV (a relative of HIV) and treated them with similar antiviral drugs that humans receive for HIV. Eight of the nine animals showed undetectable amounts of SIV in their blood so the team looked at CD4+ memory T cells, which are known to shelter the virus.
"We found that a certain group of memory CD4+ T cells displaying CTLA4, but not another co-inhibitor receptor called PD1, harbor viral DNA at higher frequencies than other groups of memory CD4+ T cells," said Mirko Paiardini, Ph.D., associate professor of pathology and laboratory medicine at Emory. "These cells can be found in multiple tissues, such as lymph node, spleen, gut and bone marrow, and contain the replication-competent and infectious virus."
Previous research had shown that HIV-infected cells persisted in regions of the lymph nodes called B cell follicles. However, working with a team led by Jacob Estes, Ph.D. at NCI/Leidos Frederick and using a technique called DNAscope, they found a group of infected cells outside the B cell follicles.
In addition, the team, with the help of Rafick Sekaly, Ph.D., at Case Western Reserve University, was able to show that CTLA4-positive PD1-negative cells have the characteristics of regulatory T cells, whose job is to put a brake on the immune system and prevent it from becoming too activated.
"It provides a strong rationale for targeting these cells," Paiardini says. "Depleting latently infected T-regs can not only reduce the reservoir but also induce a stronger antiviral immune response."
Based on the findings, Paiardini believes CTLA-4 should be considered as an additional target when designing immunotherapies aimed at purging the viral reservoir.