HIV-specific T cell responses reflect substantive in vivo interactions with antigen despite long-term therapy.
JCI Insight
; 6(3)2021 02 08.
Article
em En
| MEDLINE
| ID: mdl-33400687
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Antígenos HIV
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Infecções por HIV
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HIV-1
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Fármacos Anti-HIV
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos