ArticlePLoS pathogens2015
Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- HIV Transmission and Immunology of the Male Reproductive Tract.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- CD11c+ myeloid cells are the predominant CD4+CCR5+ immune population in the foreskin and are increased in men with HIV-associated penile anaerobes.bioRxiv : the preprint server for biology · 2026Article
- Anaerobe-Driven Inflammation and Epithelial Barrier Disruption in Genital HIV Acquisition.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- The neovaginal microbiota, symptoms, and local immune correlates in transfeminine individuals with penile inversion vaginoplasty.Cell reports · 2025Article
- PET/CT Targeted Tissue Sampling Reveals Intravenously Administered HGN194 IgG1 Affects HIV Distribution after Rectal Exposure.AIDS research and human retroviruses · 2024Article
- Article
- Comparison between a deep-learning and a pixel-based approach for the automated quantification of HIV target cells in foreskin tissue.Scientific reports · 2024Article
- Article
- TRPV1 activation in human Langerhans cells and T cells inhibits mucosal HIV-1 infection via CGRP-dependent and independent mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Infant Circumcision for Sexually Transmitted Infection Risk Reduction Globally.Global health, science and practice · 2022Article
- Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue.Pharmaceutics · 2022Article
- HIV-1-Mediated Acceleration of Oncovirus-Related Non-AIDS-Defining Cancers.Biomedicines · 2022Review
- Semen: A modulator of female genital tract inflammation and a vector for HIV-1 transmission.American journal of reproductive immunology (New York, N.Y. : 1989) · 2021Review
- Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (HCMV) Coinfection of Infant Tonsil Epithelium May Synergistically Promote both HIV-1 and HCMV Spread and Infection.Journal of virology · 2021Article
- Circumcision as an Intervening Strategy against HIV Acquisition in the Male Genital Tract.Pathogens (Basel, Switzerland) · 2021Review
- PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure.PLoS pathogens · 2021Article
- Oncogenic Effects of HIV-1 Proteins, Mechanisms Behind.Cancers · 2021Review
- Article
- Durable protection against repeated penile exposures to simian-human immunodeficiency virus by broadly neutralizing antibodies.Nature communications · 2020Article
- The cervicovaginal mucus barrier to HIV-1 is diminished in bacterial vaginosis.PLoS pathogens · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 μm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men.
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