HIV-specific T cell responses reflect substantive in vivo interactions with antigen despite long-term therapy
Open Access
- 8 February 2021
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
Abstract
Antiretroviral therapies (ARTs) abrogate HIV replication; however, infection persists as long-lived reservoirs of infected cells with integrated proviruses, which reseed replication if ART is interrupted. A central tenet of our current understanding of this persistence is that infected cells are shielded from immune recognition and elimination through a lack of antigen expression from proviruses. Efforts to cure HIV infection have therefore focused on reactivating latent proviruses to enable immune-mediated clearance, but these have yet to succeed in reducing viral reservoirs. Here, we revisited the question of whether HIV reservoirs are predominately immunologically silent from a new angle: by querying the dynamics of HIV-specific T cell responses over long-term ART for evidence of ongoing recognition of HIV-infected cells. In longitudinal assessments, we show that the rates of change in persisting HIV Nef-specific responses, but not responses to other HIV gene products, were associated with residual frequencies of infected cells. These Nef-specific responses were highly stable over time and disproportionately exhibited a cytotoxic, effector functional profile, indicative of recent in vivo recognition of HIV antigens. These results indicate substantial visibility of the HIV-infected cells to T cells on stable ART, presenting both opportunities and challenges for the development of therapeutic approaches to curing infection.Keywords
Funding Information
- National Institutes of Health (1UM1AI26617)
- National Institute of Allergy and Infectious Diseases (UM1 AI068634,UM1 AI068636,UM1 AI106701)
- National Institutes of Health (AI31798,AI147845)
- National Institutes of Health (R56AI52764)
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