Luminal microvesicles uniquely influence translocating bacteria after SIV infection

Area of Science:

• Microbiology
• Immunology
• Virology

Background:

• Microbial translocation, a key factor in HIV-associated inflammation, involves intestinal barrier dysfunction.
• A bias exists towards the translocation of Proteobacteria, suggesting specific mechanisms at play.

Purpose of the Study:

• To investigate if intestinal epithelial microvesicle cargo changes post-HIV infection and contributes to biased microbial translocation.
• To identify specific molecular differences in microvesicles that influence bacterial growth.

Main Methods:

• Isolation of gastrointestinal luminal microvesicles from rhesus macaques before and after simian immunodeficiency virus (SIV) infection.
• Measurement of microvesicle miRNA and antimicrobial peptide content.
• Co-culture experiments to assess the impact of microvesicles on commensal bacteria growth.

Main Results:

• SIV infection led to decreased levels of specific miRNAs (miR-28-5p, -484, -584-3p, -584-5p, let-7b-3p) and increased beta-defensin 1 in microvesicles.
• Isolated microvesicles from infected macaques showed dose-dependent inhibition of Lactobacillus salivarius growth.
• These changes were not observed in non-progressively infected sooty mangabeys.

Conclusions:

• Progressive SIV infection alters gut microvesicle composition, affecting antimicrobial control.
• These alterations influence the growth of bacterial taxa that may translocate across the gut barrier.
• Findings offer insights into novel therapeutic targets for HIV, microbial translocation, and chronic inflammation.