HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy
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. Furthermore, these observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.
- Authors:
-
[1];
[2];
[2];
- Univ. of North Carolina, School of Medicine, Chapel Hill, NC (United States)
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- San Diego Healthcare System, San Diego, CA (United States)
- Univ. of North Carolina, Chapel Hill, NC (United States)
- San Diego Healthcare System, San Diego, CA (United States); Univ. of California, San Diego, CA (United States)
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- National Institutes of Health (NIH); USDOE
- OSTI Identifier:
- 1414147
- Report Number(s):
- LA-UR-17-22196
Journal ID: ISSN 1078-8956; TRN: US1800670
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Medicine
- Additional Journal Information:
- Journal Volume: 23; Journal Issue: 5; Journal ID: ISSN 1078-8956
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; Biological Science
Citation Formats
Honeycutt, Jenna B., Thayer, William O., Baker, Caroline E., Ribeiro, Ruy M., Lada, Steven M., Cao, Youfang, Cleary, Rachel A., Hudgens, Michael G., Richman, Douglas D., and Garcia, J. Victor. HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. United States: N. p., 2017.
Web. doi:10.1038/nm.4319.
Honeycutt, Jenna B., Thayer, William O., Baker, Caroline E., Ribeiro, Ruy M., Lada, Steven M., Cao, Youfang, Cleary, Rachel A., Hudgens, Michael G., Richman, Douglas D., & Garcia, J. Victor. HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. United States. https://doi.org/10.1038/nm.4319
Honeycutt, Jenna B., Thayer, William O., Baker, Caroline E., Ribeiro, Ruy M., Lada, Steven M., Cao, Youfang, Cleary, Rachel A., Hudgens, Michael G., Richman, Douglas D., and Garcia, J. Victor. Mon .
"HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy". United States. https://doi.org/10.1038/nm.4319. https://www.osti.gov/servlets/purl/1414147.
@article{osti_1414147,
title = {HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy},
author = {Honeycutt, Jenna B. and Thayer, William O. and Baker, Caroline E. and Ribeiro, Ruy M. and Lada, Steven M. and Cao, Youfang and Cleary, Rachel A. and Hudgens, Michael G. and Richman, Douglas D. and Garcia, J. Victor},
abstractNote = {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. Furthermore, these observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.},
doi = {10.1038/nm.4319},
journal = {Nature Medicine},
number = 5,
volume = 23,
place = {United States},
year = {Mon Apr 17 00:00:00 EDT 2017},
month = {Mon Apr 17 00:00:00 EDT 2017}
}
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The Role of Macrophages in HIV-1 Persistence and Pathogenesis
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New Frontiers in Measuring and Characterizing the HIV Reservoir
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Beyond the replication-competent HIV reservoir: transcription and translation-competent reservoirs
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What do we measure when we measure cell-associated HIV RNA
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Host mRNA decay proteins influence HIV-1 replication and viral gene expression in primary monocyte-derived macrophages
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Human Interleukin-34 facilitates microglia-like cell differentiation and persistent HIV-1 infection in humanized mice
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Landscape review of current HIV ‘kick and kill’ cure research - some kicking, not enough killing
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Tobacco and Antiretrovirals Modulate Transporter, Metabolic Enzyme, and Antioxidant Enzyme Expression and Function in Polarized Macrophages
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Role of Monocyte/Macrophages during HIV/SIV Infection in Adult and Pediatric Acquired Immune Deficiency Syndrome
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Myeloid Cell Interaction with HIV: A Complex Relationship
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Tunneling Nanotubes: Intimate Communication between Myeloid Cells
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The HIV Reservoir in Monocytes and Macrophages
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Blocking Formation of the Stable HIV Reservoir: A New Perspective for HIV-1 Cure
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The Effects of Opioids on HIV Neuropathogenesis
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The Role of Macrophages in HIV-1 Persistence and Pathogenesis
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Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs
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Recent Updates on Mouse Models for Human Immunodeficiency, Influenza, and Dengue Viral Infections
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