| Title: |
Innate immune regulation in HIV latency models |
| Authors: |
Rebecca M. Olson, Germán Gornalusse, Leanne S. Whitmore, Dan Newhouse, Jennifer Tisoncik-Go, Elise Smith, Christina Ochsenbauer, Florian Hladik, Michael Gale |
| Source: |
Retrovirology, Vol 19, Iss 1, Pp 1-26 (2022) |
| Publisher Information: |
BMC, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
HIV, Latent infection, Reservoir, Innate immunity, Interferon, Interferon-stimulated gene, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
Abstract Background Innate immunity and type 1 interferon (IFN) defenses are critical for early control of HIV infection within CD4 + T cells. Despite these defenses, some acutely infected cells silence viral transcription to become latently infected and form the HIV reservoir in vivo. Latently infected cells persist through antiretroviral therapy (ART) and are a major barrier to HIV cure. Here, we evaluated innate immunity and IFN responses in multiple T cell models of HIV latency, including established latent cell lines, Jurkat cells latently infected with a reporter virus, and a primary CD4 + T cell model of virologic suppression. Results We found that while latently infected T cell lines have functional RNA sensing and IFN signaling pathways, they fail to induce specific interferon-stimulated genes (ISGs) in response to innate immune activation or type 1 IFN treatment. Jurkat cells latently infected with a fluorescent reporter HIV similarly demonstrate attenuated responses to type 1 IFN. Using bulk and single-cell RNA sequencing we applied a functional genomics approach and define ISG expression dynamics in latent HIV infection, including HIV-infected ART-suppressed primary CD4 + T cells. Conclusions Our observations indicate that HIV latency and viral suppression each link with cell-intrinsic defects in specific ISG induction. We identify a set of ISGs for consideration as latency restriction factors whose expression and function could possibly mitigate establishing latent HIV infection. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1742-4690 |
| Relation: |
https://doaj.org/toc/1742-4690 |
| DOI: |
10.1186/s12977-022-00599-z |
| Access URL: |
https://doaj.org/article/7d5187e961a84a13a45c635ab2745311 |
| Accession Number: |
edsdoj.7d5187e961a84a13a45c635ab2745311 |
| Database: |
Directory of Open Access Journals |
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