Abstract

MOLBA03 - Oral Abstract Session

HIV-1 female-to-male sexual transmission: evaluation of circumcised and uncircumcised penile tissue

Presented by Minh Dinh (United States).

M. Dinh¹, M. Anderson¹, C. Gioia¹, M. McRaven¹, Z. Okocha¹, G. Cianci¹, T. Hirbod², G. Kigozi³, J. Prodger⁴, R. Kaul⁴, X. Kong⁵, R. Gray⁵, T. Hope<sup>1

1</sup>Northwestern University Feinberg School of Medicine, Cell and Molecular Biology, Chicago, United States, ²Karolinska Institutet, Stockholm, Sweden, ³Rakai Health Sciences Program, Entebbe, Uganda, ⁴University of Toronto, Toronto, Canada, ⁵Johns Hopkins Bloomberg School of Public Health, Baltimore, United States

Background: Male circumcision has been shown to decrease rates of HIV acquisition in African men. The STEP vaccine trial also demonstrated that vaccinated, uncircumcised men were at increased risk for HIV acquisition. We sought to identify the mode(s) by which HIV infection may occur in uncircumcised men.
Methods: Foreskins were obtained from consenting male donors receiving prophylactic male circumcision in Rakai, Uganda. Whole penile specimens were obtained from tissue donation organizations (ScienceCare and NDRI). Using fluorescent immunohistochemistry, foreskin keratin layers were labeled with filaggrin and involucrin markers. Penile tissues were incubated with ex vivo with photo-activatable GFP-linked-Vpr HIV­­_Bal for 4 hours, snap-frozen, and cryosections stained for target cells and keratin. Images were obtained with epifluorescent microscopy and analyzed for keratin thickness, viral particles, and viral penetration into penile epithelia.
Results: We found no significant differences between inner and outer foreskin keratin layers from 19 foreskin samples obtained in Uganda, indicating that reduced keratin thickness is not likely to make the inner foreskin more susceptible to HIV. Preliminary data from whole penile specimens (uncircumcised n=7, circumcised n=7) shows no significant difference in number of visualized virions per image captured, but more virions entering uncircumcised as compared to circumcised glans tissue (uncircumcised:circumcised = 2:1). Virions were found at distances from the epithelial surface (mean ± SD = 33.5 ± 22.3 µm) in the range where CD4+ cells are also localized (mean ± SD = 53.6 ±32.3 µm), in the absence of trauma to the epithelium. Finally, we visualize virions interacting with the male urethral pseudo-stratified columnar epithelia, though to a lesser degree than seen with stratified squamous epithelia (n=5, glans:urethra=2:1).
Conclusions: These preliminary results suggest preferential routes by which HIV-1 may enter the male genital tract in female-to-male HIV sexual transmission.