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 PengJan Komorowski, Cristian Apetrei, Ivona Pandrea, Michael Gale

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number5101
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Barrenas, F., Raehtz, K., Xu, C., Law, L., Green, R. R., Silvestri, G., Bosinger, S. E., Nishida, A., Li, Q., Lu, W., Zhang, J., Thomas, M. J., Chang, J., Smith, E., Weiss, J. M., Dawoud, R. A., Richter, G. H., Trichel, A., Ma, D., ... Gale, M. (2019). Macrophage-associated wound healing contributes to African green monkey SIV pathogenesis control. Nature communications, 10(1), [5101]. https://doi.org/10.1038/s41467-019-12987-9