Cited by 370HIV Research and TreatmentVirus-based gene therapy researchT-cell and Retrovirus Studies

Defective HIV-1 proviruses are expressed and can Be recognized by cytotoxic T lymphocytes, which shape the proviral landscape

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Pollack, Ross A., Jones, R. Brad, Pertea, Mihaela, Bruner, Katherine M., Martin, Alyssa R., Thomas, Allison S., Capoferri, Adam A., Beg, Subul A. +9 more·2017·Cell Host & Microbe

Abstract

Despite antiretroviral therapy, HIV-1 persists in memory CD4+ T cells, creating a barrier to cure. The majority of HIV-1 proviruses are defective and considered clinically irrelevant. Using cells from HIV-1-infected individuals and reconstructed patient-derived defective proviruses, we show that defective proviruses can be transcribed into RNAs that are spliced and translated. Proviruses with defective major splice donors (MSDs) can activate novel splice sites to produce HIV-1 transcripts, and cells with these proviruses can be recognized by HIV-1-specific cytotoxic T lymphocytes (CTLs). Further, cells with proviruses containing lethal mutations upstream of CTL epitopes can also be recognized by CTLs, potentially through aberrant translation. Thus, CTLs may change the landscape of HIV-1 proviruses by preferentially targeting cells with specific types of defective proviruses. Additionally, the expression of defective proviruses will need to be considered in the measurement of HIV-1 latency reversal.

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Crossref · 10.1016/j.chom.2017.03.008

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  • A multitude of studies showed that defective HIV-1 genomes inside cells may still produce individual viral transcripts or proteins, which could be mistaken as indicators of a functional reservoir of infectious virus.

    “Conversely, a multitude of studies showed that defective HIV-1 genomes inside cells may still produce individual viral transcripts or proteins, 33-35,55 which could be mistaken as indicators of a functional reservoir of infectious virus.”

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Authors
Pollack, R. A., Jones, R. B., Pertea, M., Bruner, K. M., Martin, A. R., Thomas, A. S., Capoferri, A. A., Beg, S. A., Huang, S.-H., Karandish, S., Hao, H., Halper-Stromberg, E., Yong, P. C., Kovacs, C., Benko, E., Siliciano, R. F., & Ho, Y.-C.
Affiliations
  • Johns Hopkins University (US)
  • George Washington University (US)
  • Howard Hughes Medical Institute (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • University of Toronto (CA)
  • Maple Leaf Medical Clinic (CA)
Corresponding author
Ho, Ya-Chi
Venue
Cell Host & Microbe
Publisher
Elsevier BV
Published
2017-04
Volume
21
Issue
4
Pages
494-506.e4
ISSN
1931-3128 (ISSN-L)
OpenAlex
W2605860823
Cited by
370
References
5
Citations by year
2026: 29 · 2025: 36 · 2024: 35 · 2023: 50 · 2022: 40 · 2021: 40 · 2020: 50 · 2019: 43 · 2018: 38 · 2017: 9
FWCI
20.85
Type
journal article
Language
en
Open access
Locations
  • Cell Host & Microbe (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH (1R21AI118402-01, AI096113, 1U19AI096109, 1UM1AI126617)
  • CARE
  • DARE
  • BELIEVE
  • American Foundation for AIDS Research (amfAR108165-50-RGRL)
  • amfAR (amfAR109315-57-RGRL)
  • Johns Hopkins Center for AIDS Research
  • CFAR (P30AI094189)
  • DC-CFAR (P30AI087714)
  • W.W. Smith Charitable Trust
  • Gilead Sciences
  • Howard Hughes Medical Institute
  • Bill and Melinda Gates Foundation
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords
alternative splicing, HIV-1 transcription, CTL epitopes, HIV-1 latency, latency reversal, HIV-1 cure
MeSH terms
Humans, Proviruses, T-Lymphocytes, Cytotoxic, Genetic Variation, HIV-1, HIV Infections

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