Intron-containing RNA from the HIV-1 provirus activates type I interferon and inflammatory cytokines
| Autor: | Leonid Yurkovetskiy, Kyusik Kim, Jeremy Luban, Ann Dauphin, William E. Diehl, Anetta Nowosielska, Sean M. McCauley |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine viruses General Physics and Astronomy Virus Replication Proviruses Transcription (biology) Interferon lcsh:Science 0303 health sciences Multidisciplinary 030302 biochemistry & molecular biology virus diseases food and beverages Provirus 3. Good health Interferon Type I RNA splicing Cytokines RNA Viral medicine.drug Gene Expression Regulation Viral medicine.drug_class Anti-HIV Agents RNA Splicing Science 030106 microbiology Biology Article General Biochemistry Genetics and Molecular Biology Virus Cell Line 03 medical and health sciences Immune system medicine Humans 030304 developmental biology Innate immune system Macrophages fungi Intron RNA rev Gene Products Human Immunodeficiency Virus Dendritic Cells General Chemistry Virology HEK293 Cells 030104 developmental biology Immunology HIV-1 lcsh:Q Antiviral drug |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-10 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-07753-2 |
| Popis: | 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. During HIV infection, antiviral therapy can suppress viraemia to undetectable levels and hinder the progression towards AIDS; however the HIV-1 provirus can remain in long-lived CD4+ memory T cells. Here the authors show that intronic RNA from the HIV-1 provirus can induce type I interferon and inflammatory cytokine production. |
| Databáze: | OpenAIRE |
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