Distinct HIV-1 Population Structure across Meningeal and Peripheral T Cells and Macrophage Lineage Cells

Rose, Rebecca; Gonzalez-Perez, Maria Paz; Nolan, David J.; Ganta, Krishna Kumar; LaFleur, Tessa M.; Cross, Sissy; Brody, Robin M.; Lamers, Susanna L.; Luzuriaga, Katherine

doi:10.1128/spectrum.02508-22

Cited by 3 publications

(1 citation statement)

References 64 publications

(77 reference statements)

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“…Though “kick and kill” strategies have dominated the HIV cure efforts, the CNS is protected by the blood–brain barrier (BBB), which limits access of systemic drugs to this compartment. Indeed, distinct selective pressures across the CNS compared to other anatomic sites may impact viral evolution and persistence in cellular reservoirs [71]. To address this issue, novel routes of administration which have direct access to the CNS can be considered, such as intranasal drug delivery [72], as well as new systems based on electromagnetic nanoparticles presenting minimal cytotoxic effects [73].…”

Section: Central Nervous Systemmentioning

confidence: 99%

Targeting HIV persistence in the tissue

Pieren,

Benítez-Martínez,

Genescà

2024

Current Opinion in HIV and AIDS

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Purpose of review The complex nature and distribution of the HIV reservoir in tissue of people with HIV remains one of the major obstacles to achieve the elimination of HIV persistence. Challenges include the tissue-specific states of latency and viral persistence, which translates into high levels of reservoir heterogeneity. Moreover, the best strategies to reach and eliminate these reservoirs may differ based on the intrinsic characteristics of the cellular and anatomical reservoir to reach. Recent findings While major focus has been undertaken for lymphoid tissues and follicular T helper cells, evidence of viral persistence in HIV and non-HIV antigen-specific CD4+ T cells and macrophages resident in multiple tissues providing long-term protection presents new challenges in the quest for an HIV cure. Considering the microenvironments where these cellular reservoirs persist opens new venues for the delivery of drugs and immunotherapies to target these niches. New tools, such as single-cell RNA sequencing, CRISPR screenings, mRNA technology or tissue organoids are quickly developing and providing detailed information about the complex nature of the tissue reservoirs. Summary Targeting persistence in tissue reservoirs represents a complex but essential step towards achieving HIV cure. Combinatorial strategies, particularly during the early phases of infection to impact initial reservoirs, capable of reaching and reactivating multiple long-lived reservoirs in the body may lead the path.

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Section: Central Nervous Systemmentioning

confidence: 99%