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Updated: May 5, 2026
Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
Published on: December 3, 2019
HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy
Jenna B Honeycutt1, William O Thayer1, Caroline E Baker1
1Division of Infectious Diseases, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, North Carolina, USA.
Abstract:
Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA and DNA. No viral rebound was observed in the plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and no replication-competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (∼33%), a delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. These observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.
Insights
Despite antiretroviral therapy (ART), HIV can persist. This study shows HIV can persist in tissue macrophages, offering new insights into HIV reservoirs and potential eradication strategies.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Antiretroviral therapy (ART) suppresses HIV but does not eradicate it.
- HIV persistence is a major barrier to complete viral eradication.
- Tissue macrophages are implicated in HIV pathogenesis, but their role in persistence during ART is unclear.
Purpose of the Study:
- To investigate the role of tissue macrophages in HIV persistence during long-term suppressive antiretroviral therapy (ART).
- To determine if tissue macrophages harbor persistent HIV infection in vivo.
Main Methods:
- Utilized humanized myeloid-only mice (MoM) infected with HIV.
- Administered long-term suppressive ART.
- Interrupted ART and monitored for viral rebound.
- Assessed viral load, cell-associated viral RNA/DNA, and replication-competent virus in tissue macrophages.
Main Results:
- ART rapidly suppressed HIV infection in tissue macrophages, indicated by decreased plasma viral load and cell-associated viral markers.
- 67% of animals showed no viral rebound after ART interruption.
- Approximately 33% of animals exhibited delayed viral rebound, linked to persistent infection in tissue macrophages.
- No replication-competent virus was recovered from macrophages in non-rebounding animals.
Conclusions:
- This study provides the first direct evidence of HIV persistence in tissue macrophages in vivo during suppressive ART.
- Tissue macrophages can act as a reservoir for persistent HIV infection, contributing to viral persistence.
- Understanding HIV persistence in macrophages is crucial for developing strategies to eradicate the virus.
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