Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape

Ross A. Pollack, R. Brad Jones, Mihaela Pertea, Katherine M. Bruner, Alyssa R. Martin, Allison S. Thomas, Adam A. Capoferri, Subul A. Beg, Szu Han Huang, Sara Karandish, Haiping Hao, Eitan Halper-Stromberg, Patrick C. Yong, Colin Kovacs, Erika Benko, Robert F. Siliciano, Ya Chi Ho

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)494-506.e4
JournalCell Host and Microbe
Volume21
Issue number4
DOIs
StatePublished - Apr 12 2017

Fingerprint

Proviruses
Cytotoxic T-Lymphocytes
HIV-1
T-Lymphocyte Epitopes
RNA
T-Lymphocytes
Mutation

Keywords

  • alternative splicing
  • APOBEC-mediated G-to-A hypermutations
  • cell-associated HIV-1 RNA
  • cold-target inhibition
  • cytotoxic T lymphocytes
  • defective HIV-1 proviruses
  • defective ribosomal product
  • HIV-1 cure
  • HIV-1 latent reservoir
  • HIV-1 proviral landscape

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology and Microbiology(all)
  • Cancer Research

Cite this

Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape. / Pollack, Ross A.; Jones, R. Brad; Pertea, Mihaela; Bruner, Katherine M.; Martin, Alyssa R.; Thomas, Allison S.; Capoferri, Adam A.; Beg, Subul A.; Huang, Szu Han; Karandish, Sara; Hao, Haiping; Halper-Stromberg, Eitan; Yong, Patrick C.; Kovacs, Colin; Benko, Erika; Siliciano, Robert F.; Ho, Ya Chi.

In: Cell Host and Microbe, Vol. 21, No. 4, 12.04.2017, p. 494-506.e4.

Research output: Contribution to journalArticle

Pollack, RA, Jones, RB, Pertea, M, Bruner, KM, Martin, AR, Thomas, AS, Capoferri, AA, Beg, SA, Huang, SH, Karandish, S, Hao, H, Halper-Stromberg, E, Yong, PC, Kovacs, C, Benko, E, Siliciano, RF & Ho, YC 2017, 'Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape' Cell Host and Microbe, vol 21, no. 4, pp. 494-506.e4. DOI: 10.1016/j.chom.2017.03.008

Pollack, Ross A.; Jones, R. Brad; Pertea, Mihaela; Bruner, Katherine M.; Martin, Alyssa R.; Thomas, Allison S.; Capoferri, Adam A.; Beg, Subul A.; Huang, Szu Han; Karandish, Sara; Hao, Haiping; Halper-Stromberg, Eitan; Yong, Patrick C.; Kovacs, Colin; Benko, Erika; Siliciano, Robert F.; Ho, Ya Chi / Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape.

In: Cell Host and Microbe, Vol. 21, No. 4, 12.04.2017, p. 494-506.e4.

Research output: Contribution to journalArticle

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