Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Biological Factors | Cells | Immune System Diseases | Immunity | Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Nucleic Acids, Nucleotides, and Nucleosides | Therapeutics | Virus Diseases | Viruses
HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, HIV-1 establishes proviruses in long-lived CD4(+) memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Here we show that the HIV-1 provirus activates innate immune signaling in isolated dendritic cells, macrophages, and CD4(+) T cells. Immune activation requires transcription from the HIV-1 provirus and expression of CRM1-dependent, Rev-dependent, RRE-containing, unspliced HIV-1 RNA. If rev is provided in trans, all HIV-1 coding sequences are dispensable for activation except those cis-acting sequences required for replication or splicing. Our results indicate that the complex, post-transcriptional regulation intrinsic to HIV-1 RNA is detected by the innate immune system as a danger signal, and that drugs which disrupt HIV-1 transcription or HIV-1 RNA metabolism would add qualitative benefit to current antiviral drug regimens.
HIV-1, innate immune signaling, immune activation
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Copyright © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
Nat Commun. 2018 Dec 13;9(1):5305. doi: 10.1038/s41467-018-07753-2. Link to article on publisher's site
McCauley, Sean M.; Kim, Kyusik; Nowosielska, Anetta; Dauphin, Ann; Yurkovetskiy, Leonid; Diehl, William E.; and Luban, Jeremy, "Intron-containing RNA from the HIV-1 provirus activates type I interferon and inflammatory cytokines" (2018). Open Access Articles. 3688.
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This work is licensed under a Creative Commons Attribution 4.0 License.
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