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Title: 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:
ORCiD logo [1];  [1];  [1]; ORCiD logo [2];  [3]; ORCiD logo [2];  [1];  [4];  [5];  [1]
  1. Univ. of North Carolina, School of Medicine, Chapel Hill, NC (United States)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  3. San Diego Healthcare System, San Diego, CA (United States)
  4. Univ. of North Carolina, Chapel Hill, NC (United States)
  5. San Diego Healthcare System, San Diego, CA (United States); Univ. of California, San Diego, CA (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (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:
Journal Article: 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. 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., and Garcia, J. Victor. Mon . "HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy". United States. doi: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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Cited by: 22works
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