Immune targeting of HIV-1 reservoir cells: a path to elimination strategies and cure

Armani-Tourret, Marie; Bone, Benjamin; Tan, Toong Seng; Sun, Weiwei; Bellefroid, Maxime; Struyve, Tine; Louella, Michael; Yu, Xu G.; Lichterfeld, Mathias

doi:10.1038/s41579-024-01010-8

Cited by 4 publications

(1 citation statement)

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“…Elite controllers are well documented as possessing potent cellular immune responses, which may be involved in these immunological selection processes. Potential immune responses that are recorded within ECs and could be ascribed to their controlling phenotype are elegantly reviewed in the literature [52][53][54][55]. Nevertheless, we are acknowledging that there is still a high degree of uncertainty surrounding the immune mechanism driving these selection processes, with further concerted investigation needed to remedy this.…”

Section: Etiology Of Distinct Integration Site Profiles In Elite Cont...mentioning

confidence: 99%

“Block and lock” viral integration sites in persons with drug-free control of HIV-1 infection

Bone,

Lichterfeld

2024

Current Opinion in HIV and AIDS

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Purpose of review Elite controllers (ECs) and Posttreatment controllers (PTCs) represent a small subset of individuals who are capable of maintaining drug-free control of HIV plasma viral loads despite the persistence of a replication-competent viral reservoir. This review aims to curate recent experimental studies evaluating viral reservoirs that distinguish EC/PTC and may contribute to their ability to maintain undetectable viral loads in the absence of antiretroviral therapy. Recent findings Recent studies on ECs have demonstrated that integration sites of intact proviruses in EC/PTC are markedly biased towards heterochromatin regions; in contrast, intact proviruses in accessible and permissive chromatin were profoundly underrepresented. Of note, no such biases were noted when CD4+ T cells from EC were infected directly ex vivo, suggesting that the viral reservoir profile in EC is not related to altered integration site preferences during acute infection, but instead represents the result of immune-mediated selection mechanisms that can eliminate proviruses in transcriptionally-active euchromatin regions while promoting preferential persistence of intact proviruses in nonpermissive genome regions. Proviral transcription in such “blocked and locked” regions may be restricted through epigenetic mechanisms, protecting them from immune-recognition but presumably limiting their ability to drive viral rebound. While the exact immune mechanisms driving this selection process remain undefined, recent single-cell analytic approaches support the hypothesis that HIV reservoir cells are subject to immune selection pressure by host factors. Summary A “blocked and locked” viral reservoir profile may constitute a structural virological correlate of a functional cure of HIV-1 infection. Further research into the immunological mechanism promoting HIV-1 reservoir selection and evolution in EC/PTC is warranted and could inform foreseeable cure strategies.

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Section: Etiology Of Distinct Integration Site Profiles In Elite Cont...mentioning

confidence: 99%