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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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 SM, Kim K, Nowosielska A, Dauphin A, Yurkovetskiy L, Diehl WE, Luban J. (2018). Intron-containing RNA from the HIV-1 provirus activates type I interferon and inflammatory cytokines. Open Access Articles. https://doi.org/10.1038/s41467-018-07753-2. Retrieved from https://escholarship.umassmed.edu/oapubs/3688
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