Journal
TRENDS IN IMMUNOLOGY
Volume 43, Issue 8, Pages 608-616Publisher
CELL PRESS
DOI: 10.1016/j.it.2022.06.002
Keywords
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Categories
Funding
- National Institutes of Health (NIH) [AI135940, AI114235, AI117841, AI120008, AI152979, AI130005, DK120387, K24 AI155233]
- amfAR [110181-69-RGCV]
- Campbell Foundation
- NIH [AI078799, DA047034, AI155171, AI150396, 110393-72-RPRL, INV-002703]
- amfAR ARCHE Grant [UM1 AI164560]
- Bill and Melinda Gates Foundation [AI164562]
- [HL134539]
- [AI116228]
- [AI164566]
- [AI164570]
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This opinion article proposes a more dynamic interpretation of HIV-1 reservoir cell biology, suggesting that HIV-1 proviruses frequently display residual viral transcriptional activity, making them vulnerable to immune-mediated selection processes. The authors suggest that intensifying and accelerating naturally occurring selection mechanisms might represent a promising strategy for finding a potential cure for HIV-1 infection.
With more than 38 million people living with HIV-1 (PLWH) worldwide, developing a cure for HIV-1 remains a major global health priority. Lifelong persistence of HIV-1 is frequently attributed to a pool of stable, transcriptionally silent HIV-1 proviruses, which are unaffected by currently available antiretroviral therapy (ART) or host immune activity. In this opinion article, we propose a more dynamic interpretation of HIV-1 reservoir cell biology and argue that HIV-1 proviruses frequently display residual viral transcriptional activity, making them vulnerable to longitudinal immune-mediated selection processes. Such mechanisms may, over extended periods of ART, induce an attenuated viral reservoir profile characterized by intact proviruses preferentially integrated into heterochromatin locations. We suggest that intensifying and accelerating naturally occurring selection mechanisms might represent a promising strategy for finding a potential cure for HIV-1 infection.
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