July 19, 2019  |  

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

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

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. Copyright © 2017 Elsevier Inc. All rights reserved.

Journal: Cell host & microbe
DOI: 10.1016/j.chom.2017.03.008
Year: 2017

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