Next Article in Journal
Deficiency of IFNAR1 Increases the Production of Influenza Vaccine Viruses in MDCK Cells
Previous Article in Journal
New Isolates of Betachloroviruses Shed Light on the Diversity and Biological Complexity of an Unexplored Group of Giant Algal Viruses
Previous Article in Special Issue
Age Matters: Key Contributors to Interferon Toxicity in Infants During Influenza Virus Infection
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Viruses
Volume 17
Issue 8
10.3390/v17081099
viruses-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Persistent Type I Interferon Signaling Impairs Innate Lymphoid Cells During HIV-1 Infection Under Suppressive ART

by
Runpeng Han
1,
Haisheng Yu
2,3,
Guangming Li
2,4,
Lishan Su
2,4,* and
Liang Cheng
1,2,5,*
1
State Key Laboratory of Virology and Biosafety, Department of Infectious Diseases, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China
2
Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3
Infectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou 510440, China
4
Division of Virology, Pathogenesis, and Cancer, Institute of Human Virology, Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
5
Center for AIDS Research, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
*
Authors to whom correspondence should be addressed.
Viruses 2025, 17(8), 1099; https://doi.org/10.3390/v17081099
Submission received: 23 June 2025 / Revised: 3 August 2025 / Accepted: 6 August 2025 / Published: 8 August 2025
(This article belongs to the Special Issue Interferon Signaling in Viral Pathogenesis)
Versions Notes

Abstract

Persistent type I interferon (IFN-I) signaling compromises adaptive anti-HIV-1 T cell immunity and promotes viral reservoir persistence, yet its effects on innate lymphoid cells during chronic infection remain unclear. Through integrated single-cell RNA sequencing and functional validation in HIV-1-infected humanized mice with combination antiretroviral therapy (cART) and IFN-I signaling blockade, we reveal IFN-I-induced dysfunction of natural killer (NK) cells and group 3 innate lymphoid cells (ILC3s). Mechanistically, the IFN-I-CD9 axis drives NK cells toward a decidual NK cell-like phenotype, impairing their cytotoxic activity. Furthermore, IFNAR blockade rescues ILC3 functionality, which is critical for IL-17/IL-22-mediated antimicrobial defense and mucosal barrier maintenance. Our study delineates IFN-I-driven immunosuppression across innate lymphocyte compartments and proposes the targeted modulation of this pathway to enhance antiviral and mucosal immunity in HIV-1 management.
Keywords: Human immunodeficiency virus; Type-I interferon; Immunopathogenesis; Innate lymphoid cells; Humanized mice Human immunodeficiency virus; Type-I interferon; Immunopathogenesis; Innate lymphoid cells; Humanized mice

Share and Cite

MDPI and ACS Style

Han, R.; Yu, H.; Li, G.; Su, L.; Cheng, L. Persistent Type I Interferon Signaling Impairs Innate Lymphoid Cells During HIV-1 Infection Under Suppressive ART. Viruses 2025, 17, 1099. https://doi.org/10.3390/v17081099

AMA Style

Han R, Yu H, Li G, Su L, Cheng L. Persistent Type I Interferon Signaling Impairs Innate Lymphoid Cells During HIV-1 Infection Under Suppressive ART. Viruses. 2025; 17(8):1099. https://doi.org/10.3390/v17081099

Chicago/Turabian Style

Han, Runpeng, Haisheng Yu, Guangming Li, Lishan Su, and Liang Cheng. 2025. "Persistent Type I Interferon Signaling Impairs Innate Lymphoid Cells During HIV-1 Infection Under Suppressive ART" Viruses 17, no. 8: 1099. https://doi.org/10.3390/v17081099

APA Style

Han, R., Yu, H., Li, G., Su, L., & Cheng, L. (2025). Persistent Type I Interferon Signaling Impairs Innate Lymphoid Cells During HIV-1 Infection Under Suppressive ART. Viruses, 17(8), 1099. https://doi.org/10.3390/v17081099

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop