SIV susceptibility in the female genital tract of adolescent versus adult pigtail macaques
Charlene Miller1, Mariluz Arainga3, Ernesto Coronado2, Tiffany Hensley-McBain1, Jennifer Manuzak1,2, Alicia Berard4, Adam Burgener4, Thomas J Hope5, Francois Villinger3, Nichole R Klatt1
1Department of Pediatrics, University of Miami, Miami, FL, USA
2Washington National Primate research Center, University of Washington, Seattle, WA, USA
3New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA
4Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
5Department of Cell & Molecular Biology, Northwestern University, Chicago, IL, USA
In southern Africa, young women aged 15-24 contribute to nearly 30% of all new HIV infections. Although social, high-risk behavioral, access to healthcare services, and economic factors all contribute to increased HIV susceptibility in young women, biological factors are thought to play a significant role. Here, we use the pigtail macaque (PTM) model to investigate signatures of susceptibility in the female genital tract (FGT) of adolescent versus adults, in hopes to develop an adolescent NHP model to test altered susceptibility to HIV infection.
Comprehensive FGT samples were collected across the menstrual cycle over a two-month period in 10 adult and 10 adolescent PTMs, followed by multiple low-dose (LD) intravaginal SIV challenges. Flow cytometry was performed on vaginal biopsies to assess frequency and phenotype of HIV target cells. Inflammatory markers were measured from cervicovaginal cytobrush supernatant via Luminex assay. 16S sequencing was performed on vaginal swabs throughout the sex cycle leading up to SIV challenges.
Our model identified no significant differences in SIV susceptibility to LD intravaginal challenges between adolescent and adults PTMs. No significant differences in HIV target cells were detected in the vaginal tissue of adolescent and adult PTMs. Although, significantly more HLA-DR+ CD20+ B cells in the vagina were detected in adolescent PTMs when compared to adults (p= 0.0435). In contrast, significantly more CD8+ T cells were detected in adult PTMs (p= 0.0369). Several inflammatory markers assessed from cervicovaginal cytobrush supernatant were higher in the adult PTMs compared to adolescents such as, sCD40L, MCP-1, IL-12p40 and TNFa (p=0.0220, p=0.0041, p=0.0789, p=0.0789 respectively). Significant microbial community differences were detected between adolescent and adult PTMs.
Our PTM model did not reveal the enhanced HIV susceptibility that is seen in adolescent females, which is supported by our negative data of any mucosal characteristics of increased SIV susceptibility in adolescent PTMs. A validated SIV NHP model of HIV infection in adolescents is currently absent and is critically needed due to the ethical challenges of enrolling women under 18 years of age in HIV clinical trials. Further validation in the FGT of NHPs is critical in better understanding vaginal transmission and increased susceptibility in adolescent females.