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Updated: May 8, 2026
09:54
Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
Published on: December 3, 2019
Distinct phases of immune system programming during ART-suppressed immunodeficiency virus infection
Maanasa Kaza1, Benjamin Varco-Merth2, G W McElfresh1
1Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, 97006, USA.
Biorxiv : the Preprint Server for Biology
|May 7, 2026
Summary
Chronic immune activation persists in people living with HIV (PLWH) even with suppressive antiretroviral therapy (ART). This study reveals biphasic immune changes during long-term ART, impacting specific tissues and cell types.
Area of Science:
- Immunology
- Virology
- Genomics
Background:
- People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) experience non-AIDS complications due to chronic immune activation.
- Understanding immune perturbations during ART-suppressed infection is crucial for managing long-term health outcomes.
Purpose of the Study:
- To define immune system changes in rhesus macaques during long-term SIV infection and ART treatment.
- To identify specific tissues and cell populations exhibiting immune dysregulation.
Main Methods:
- Longitudinal single-cell transcriptomic analysis.
- Plasma proteomic analysis of SIV-infected rhesus macaques under ART for 70 weeks.
Main Results:
- Identified broad, bi-phasic immune changes, including an early interferon-driven signature that resolved with viral control.
- Observed blunted interferon response in gut-associated lymph nodes, potentially contributing to viral reservoir persistence.
- Detected later alterations (54-66 weeks post-infection) involving TGF-β and NF-κB signaling and inflammatory monocytes in bone marrow.
Conclusions:
- Long-term ART-suppressed HIV infection involves biphasic immune remodeling.
- Specific tissues and cell populations show persistent immune dysregulation, offering targets for future therapeutic interventions.
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