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Macrophage-associated wound healing contributes to African green monkey SIV pathogenesis control
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA USA;Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA.
Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA.
Univ Washington, Dept Immunol, Seattle, WA 98195 USA;Univ Washington, Ctr Innate Immun & Immune Dis, Seattle, WA 98195 USA.
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2019 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 5101Article in journal (Refereed) Published
Abstract [en]

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-beta 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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 10, article id 5101
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Microbiology
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URN: urn:nbn:se:uu:diva-398033DOI: 10.1038/s41467-019-12987-9ISI: 000495393400001PubMedID: 31704931OAI: oai:DiVA.org:uu-398033DiVA, id: diva2:1375071
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Swedish Research Council, D0045701eSSENCE - An eScience CollaborationAvailable from: 2019-12-04 Created: 2019-12-04 Last updated: 2019-12-04Bibliographically approved

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