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African green monkeys avoid SIV disease progression by preventing intestinal dysfunction and maintaining mucosal
Kevin D Raehtz1, Fredrik Barrenäs2,3, Cuiling Xu1,4
1Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Plos Pathogens
|March 3, 2020
Summary
African green monkeys (AGMs) infected with simian immunodeficiency virus (SIV) maintain gut integrity, preventing microbial translocation and inflammation. This study confirms preserved gut epithelial integrity in AGMs during early SIV infection, offering insights into nonpathogenic SIV infection.
Area of Science:
- Virology
- Immunology
- Gastroenterology
Background:
- Simian immunodeficiency virus (SIV) infection is nonpathogenic in African green monkeys (AGMs), unlike human immunodeficiency virus (HIV) in humans.
- AGMs resist SIV-induced disease progression by preventing gut dysfunction, microbial translocation, and immune activation.
- Mechanisms preserving gut integrity in SIV-infected AGMs remain largely unknown.
Purpose of the Study:
- To investigate early events of SIV infection in AGMs.
- To examine the impact of SIVsab infection on the gut mucosa and identify mechanisms of gut integrity preservation.
Main Methods:
- Intrarectal infection of 29 adult male AGMs with SIVsab92018.
- Serial sacrifice at defined stages: preramp-up (1-3 dpi), ramp-up (4-6 dpi), peak viremia (9-12 dpi), and early chronic infection (46-55 dpi).
- Assessment of immune activation, apoptosis, epithelial damage, microbial translocation, viral loads, cytokines, and gut dysfunction markers; RNAseq of gut tissue.
Main Results:
- A transient, interferon-based inflammatory response was observed.
- No significant increase in plasma markers of enteropathy, apoptosis, or mucosal epithelial damage during early SIVsab infection.
- RNAseq confirmed no significant gene expression alterations indicating microbial translocation.
- Gut epithelial integrity was preserved throughout early SIVsab infection in AGMs.
Conclusions:
- AGMs maintain gut epithelial integrity and avoid microbial translocation during early SIV infection.
- Preserved gut integrity may protect AGMs from intestinal dysfunction and chronic inflammation.
- Findings provide insights into mechanisms of nonpathogenic SIV infection and potential implications for HIV/AIDS research.
