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Laura Romas (MSc . Student) Burgener Lab, University of Manitoba, Canada

HIV-Exposed Seronegative Men who have Sex with Men overexpress potential antiviral antiproteases in their rectal mucosa. Laura Romas (MSc . Student) Burgener Lab, University of Manitoba, Canada. Why is the rectal mucosa so susceptible to HIV infection?. 1. Thin epithelial layer.

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Laura Romas (MSc . Student) Burgener Lab, University of Manitoba, Canada

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  1. HIV-Exposed Seronegative Men who have Sex with Men overexpress potential antiviral antiproteases in their rectal mucosa Laura Romas (MSc. Student) Burgener Lab, University of Manitoba, Canada

  2. Why is the rectal mucosa so susceptible to HIV infection? 1. Thin epithelial layer 4. Mucosal Fluid? 2. Many HIV target cells 3. Easily accessible lymphatic system GALT

  3. Natural Immunity in HIV Exposed Seronegative (HESN) Individuals • HESN MSM from the Venhälsan Cohort (est. 2007): • Gay Men`s Health Clinic in Stockholm, Sweden. • Serodiscordant couples >5yrs • Men have HIV neutralizing IgA within their mucosal fluid, but no HIV antibodies in serum • (Hasselrotet al. AIDS. 2009) HIV Exposed Seronegative HIV + Partner

  4. Using Proteomics to Identify Correlates of Protection A. Mucosal Fluid Peptides ID/ Quant Targets HESN vs. Control (n=23) (n=20) B. Target P24

  5. HESN MSM over-express several immune proteins in their mucosal fluid Intelectin 2 α-1-acid glycoprotein 1 Antiprotease 1 S100A7 Antiprotease 2 Antirpotease S100A9 S100A8 α -1-acid glycoprotein 1 Myeloperoxidase Ig Heavy chain Immunoglobulin Immunoglobulin Immunoglobulin Immunoglobulin Immunoglobulin Immunoglboulin Immunoglobulin Tetraspanin 8 * 80% power (≥2 fold difference), p<0.05, Benjimani-Hochberg corrected

  6. Antiproteases in Immunity AP 1 (Log2 Rel. Abund.) AP 2 (Log2 Rel. Abund.) **p<0.001

  7. Epidemiological Correlations • Antiprotease expression does not correlate with: • Vial exposure (viral load of HIV+ partner) • Mucosal response to HIV (HIV-neutralizing IgA) • Seminal/microbial exposure from unprotected intercourse (Frequency of unprotected sex)

  8. AP1 inhibits infection in PBMCs A. B. P>0.01 P>0.01 P>0.01 P>0.01 P>0.01 P>0.01 P<0.01 P<0.01 C. D.

  9. Conclusions • HESN MSM overexpress antiproteases • AP expression does not correlate with exposure • AP1 show antiviral properties in vitro • PBMC culture • Maintains cell viability • Future Directions: • Follow up in colorectal explants (underway) • Antiviral mechanism • Application: • Increase knowledge of HIV pathogenesis through the rectum • Guide future microbicide research

  10. Acknowledgements Mentors Adam Burgener and Blake Ball; Kevin Coombs and Emmanuel Ho Carolina Herrerra(Imperial College of London, Shattock Lab) University of Manitoba, HIV Research Group, Canada Lindsay Aboud, Melissa Herman, Sue Ramdahin, Kenzie Birse, Max Abou, DerekStein, Michelle Perner, Jen Butler and LianeArcinas National Microbiology Laboratory, Canada Frank Plummer; Garrett Westmacott, Stuart McCorrister and Patrick Chong KarolinskaInstitutet, Sweden KristinalBroliden, KlaraHasselrot, A. Tjerlund, P. Levinson, L. Persson, P. Saberg, G. Bratt, E. Sandstrom MSM / HESN Participants of the Gay Men’s Health Clinic, Stockholm, SWD.

  11. AP1 inhibits HIV infection in TZM-blcells A. B. C. D.

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