HIV and its simian counterpart, SIV, infect and kill CD4 T cells in the immune system, resulting in a massive depletion that ultimately leads to AIDS in the absence of antiretroviral therapy (ART). With effective therapy, CD4 T cells are largely preserved, but some harbor latent virus that can persist for decades and reemerge when ART is interrupted, presenting a hurdle to curing HIV.
Despite the significance of CD4 T cells in HIV disease progression, detailed characterization of infected cells has been unavailable. A new study led by the U.S. Military HIV Research Program (MHRP) used novel single-cell technologies to build the first profile of SIV-infected cells from infected animals to inform future therapeutic strategies. Findings were published earlier this week in PLOS Pathogens.
“To prevent or eliminate infection at the cellular level, we need to identify factors, such as proteins, expressed by these CD4 T cells, which may serve as unique biomarkers or drug targets,” said Dr. Diane Bolton, MHRP’s Chief of Animal Models and Pathogenesis, and co-author of the publication.
Viral interactions within host cells can vary based on multiple factors, including the genetic makeup of the host, and these variations can impact mechanisms of viral replication and immune evasion. Cells expressing the most virus were surprisingly diverse, comprised of both activated and non-activated states and often retaining expression of proteins known to be targeted by the virus.
“Given the remarkable phenotypic diversity of infected cells observed here, therapeutic strategies that aim to target infected cells must address an eclectic mix of CD4 T cells,” said Bolton. “The more we understand about these complex interactions, the better we can focus our efforts.”