Diversity of HIV-1 reservoirs in CD4+ T-cell subpopulations

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Purpose of review

HIV-1 is able to create lasting reservoirs of virally infected cells that persist life-long and are extremely difficult to eradicate, thus necessitating indefinite antiretroviral therapy. Large numbers of studies suggest that CD4+ T cells represent the major, and possibly the only cell type supporting HIV-1 long-term persistence. However, the ability to serve as long-term viral reservoirs may be confined to certain subpopulations of CD4+ T cells with specific functional and developmental characteristics that HIV-1 can selectively exploit to propagate long-term viral survival within the host. Identification of CD4+ T-cell subtypes that serve as hotspots for viral persistence may be critical for designing strategies to purge the immune system of persisting viral reservoirs.

Recent findings

Developmentally immature, long-lasting CD4+ memory T-cell populations seem to contain the majority of latently HIV-1-infected cells that persist despite antiretroviral therapy in the peripheral blood. Emerging data suggest that functional polarization toward a T helper 17 (Th17), a T follicular helper cell or a regulatory T-cell lineage may also be associated with an increased ability to serve as a viral reservoir site. Atypical T cells such a γδ CD4+ T cells or tissue-resident memory CD4+ T cells may be predestined to serve as sites for HIV-1 persistence in specific tissues, but will require additional exploration in future studies.


Recent advances have increased awareness for the profound diversity and complexity of CD4+ T-cell subpopulations serving as sites for HIV-1 persistence. Continuous technological and methodological improvements to interrogate viral reservoirs in distinct CD4+ T-cell subpopulations may allow to define a more complete landscape of the HIV-1 reservoir composition in different T-cell subpopulations.

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