Innate immune regulation in HIV latency models.
HIV
Immune escape
Innate immunity
Interferon
Interferon-stimulated gene
Latent infection
RIG-I
Reservoir
Journal
Retrovirology
ISSN: 1742-4690
Titre abrégé: Retrovirology
Pays: England
ID NLM: 101216893
Informations de publication
Date de publication:
08 07 2022
08 07 2022
Historique:
received:
15
04
2022
accepted:
25
05
2022
entrez:
8
7
2022
pubmed:
9
7
2022
medline:
14
7
2022
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 35804422
doi: 10.1186/s12977-022-00599-z
pii: 10.1186/s12977-022-00599-z
pmc: PMC9270781
doi:
Substances chimiques
Antiviral Agents
0
Interferon Type I
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
15Subventions
Organisme : NIH HHS
ID : P51 OD010425
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA040386
Pays : United States
Organisme : NIH HHS
ID : R01AI127563
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116292
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR002317
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI118916
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI151698
Pays : United States
Informations de copyright
© 2022. The Author(s).
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