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

Fredrik Barrenas, Kevin Raehtz, Cuiling Xu, Lynn Law, Richard R. Green, Guido Silvestri, Steven E. Bosinger, Andrew Nishida, Qingsheng Li, Wuxun Lu, Jianshui Zhang, Matthew J. Thomas, Jean Chang, Elise Smith, Jeffrey M. Weiss, Reem A. Dawoud, George H. Richter, Anita Trichel, Dongzhu Ma, Xinxia Peng, Jan Komorowski, Cristian Apetrei, Ivona Pandrea and Michael Gale ()
Additional contact information
Fredrik Barrenas: University of Washington
Kevin Raehtz: University of Pittsburgh
Cuiling Xu: University of Pittsburgh
Lynn Law: University of Washington
Richard R. Green: University of Washington
Guido Silvestri: Emory University
Steven E. Bosinger: Emory University
Andrew Nishida: University of Washington
Qingsheng Li: University of Nebraska-Lincoln
Wuxun Lu: University of Nebraska-Lincoln
Jianshui Zhang: University of Nebraska-Lincoln
Matthew J. Thomas: University of Washington
Jean Chang: University of Washington
Elise Smith: University of Washington
Jeffrey M. Weiss: University of Washington
Reem A. Dawoud: Emory University
George H. Richter: University of Pittsburgh
Anita Trichel: University of Pittsburgh
Dongzhu Ma: University of Pittsburgh
Xinxia Peng: North Carolina State University
Jan Komorowski: Uppsala University
Cristian Apetrei: University of Pittsburgh
Ivona Pandrea: University of Pittsburgh
Michael Gale: University of Washington

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12987-9

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