CD8+ cells and small viral reservoirs facilitate post-ART control of SIV in Mauritian cynomolgus macaques.
Olivia E HarwoodLea M MatschkeRyan V MoriartyAlexis J BalgemanAbigail J WeaverAmy L Ellis-ConnellAndrea M WeilerLee C WinchesterCourtney V FletcherThomas C FriedrichBrandon F KeeleDavid H O'ConnorJessica D LangMatthew R ReynoldsShelby L O ConnorPublished in: bioRxiv : the preprint server for biology (2023)
Sustainable HIV remission after antiretroviral therapy (ART) withdrawal, or post-treatment control (PTC), remains a top priority for HIV treatment. We observed surprising PTC in an MHC-haplomatched cohort of MHC-M3+ SIVmac239+ Mauritian cynomolgus macaques (MCMs) initiated on ART at two weeks post-infection (wpi). For six months after ART withdrawal, we observed undetectable or transient viremia in seven of eight MCMs. In vivo depletion of CD8α+ cells induced rebound in all animals, indicating the PTC was mediated, at least in part, by CD8α+ cells. We found that MCMs had smaller acute viral reservoirs than a cohort of identically infected rhesus macaques, a population that rarely develops PTC. The mechanisms by which unusually small viral reservoirs and CD8α+ cell-mediated virus suppression enable PTC can be investigated using this MHC-haplomatched MCM model. Further, defining the immunologic mechanisms that engender PTC in this model may identify therapeutic targets for inducing durable HIV remission in humans.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- human immunodeficiency virus
- induced apoptosis
- hiv aids
- hiv infected patients
- cell cycle arrest
- sars cov
- hepatitis c virus
- hiv testing
- endoplasmic reticulum stress
- signaling pathway
- oxidative stress
- single cell
- nk cells
- stem cells
- single molecule
- cell death
- liver failure
- extracorporeal membrane oxygenation
- diabetic rats
- combination therapy
- systemic lupus erythematosus
- south africa
- pi k akt
- high speed
- stress induced
- endothelial cells
- atomic force microscopy
- respiratory failure
- high glucose