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Nat Commun. 2019 Nov 8;10(1):5101. doi: 10.1038/s41467-019-12987-9.

Macrophage-associated wound healing contributes to African green monkey SIV pathogenesis control.

Author information

1
Department of Microbiology, University of Washington, Seattle, WA, USA.
2
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
3
Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
4
Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
5
Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
6
Department of Immunology, University of Washington, Seattle, WA, USA.
7
Center for Innate Immunity and Immune Diseases, University of Washington, Seattle, WA, USA.
8
Department of Pathology & Laboratory Medicine, Emory University, Atlanta, GA, USA.
9
Division of Microbiology & Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
10
Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.
11
Washington National Primate Research Center, University of Washington, Seattle, WA, USA.
12
Divison of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, PA, USA.
13
Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
14
Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA.
15
Department of Immunology, University of Washington, Seattle, WA, USA. mgale@uw.edu.
16
Center for Innate Immunity and Immune Diseases, University of Washington, Seattle, WA, USA. mgale@uw.edu.
17
Washington National Primate Research Center, University of Washington, Seattle, WA, USA. mgale@uw.edu.

Abstract

Natural hosts of simian immunodeficiency virus (SIV) avoid AIDS despite lifelong infection. Here, we examined how this outcome is achieved by comparing a natural SIV host, African green monkey (AGM) to an AIDS susceptible species, rhesus macaque (RM). To asses gene expression profiles from acutely SIV infected AGMs and RMs, we developed a systems biology approach termed Conserved Gene Signature Analysis (CGSA), which compared RNA sequencing data from rectal AGM and RM tissues to various other species. We found that AGMs rapidly activate, and then maintain, evolutionarily conserved regenerative wound healing mechanisms in mucosal tissue. The wound healing protein fibronectin shows distinct tissue distribution and abundance kinetics in AGMs. Furthermore, AGM monocytes exhibit an embryonic development and repair/regeneration signature featuring TGF-β and concomitant reduced expression of inflammatory genes compared to RMs. This regenerative wound healing process likely preserves mucosal integrity and prevents inflammatory insults that underlie immune exhaustion in RMs.

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