Macrophage-associated wound healing contributes to African green monkey SIV pathogenesis control
Fredrik Barrenas1,2, Kevin Raehtz3,4, Cuiling Xu5
1Department of Microbiology, University of Washington, Seattle, WA, USA.
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.
Insights
African green monkeys (AGMs) resist simian immunodeficiency virus (SIV) by activating conserved wound healing mechanisms. This process, involving fibronectin and TGF-β, prevents immune exhaustion seen in AIDS-susceptible rhesus macaques (RMs).
Area of Science:
- Immunology
- Virology
- Systems Biology
Background:
- Natural hosts of simian immunodeficiency virus (SIV) avoid AIDS despite lifelong infection.
- Rhesus macaques (RMs) are susceptible to simian AIDS.
- African green monkeys (AGMs) are natural SIV hosts that do not develop AIDS.
Purpose of the Study:
- To investigate the mechanisms by which AGMs resist SIV-induced immunodeficiency.
- To compare gene expression profiles in SIV-infected AGMs and RMs.
Main Methods:
- Developed Conserved Gene Signature Analysis (CGSA), a systems biology approach.
- Compared RNA sequencing data from rectal tissues of SIV-infected AGMs and RMs.
- Analyzed gene expression profiles, focusing on wound healing and immune response pathways.
Main Results:
- AGMs rapidly activate and maintain conserved, evolutionarily regenerative wound healing mechanisms in mucosal tissue.
- Fibronectin, a wound healing protein, exhibits distinct tissue distribution and abundance kinetics in AGMs.
- AGM monocytes display an embryonic development and repair/regeneration signature with reduced inflammatory gene expression compared to RMs, featuring TGF-β.
Conclusions:
- AGMs employ a regenerative wound healing process to maintain mucosal integrity during SIV infection.
- This regenerative response likely prevents the inflammatory insults that lead to immune exhaustion in SIV-susceptible species like RMs.
- The findings offer insights into host-pathogen interactions and potential strategies for preventing SIV/HIV pathogenesis.
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