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Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission

Dinh, Minh H., Anderson, Meegan R., McRaven, Michael D., Cianci, Gianguido C., McCoombe, Scott G., Kelley, Z. L., Gioia, Casey J., Fought, Angela J., Rademaker, Alfred W., Veazey, Ronald S. and Hope, Thomas J. 2015, Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission, PLoS pathogens, vol. 11, no. 3, pp. 1-20, doi: 10.1371/journal.ppat.1004729.

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Title Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission
Author(s) Dinh, Minh H.
Anderson, Meegan R.
McRaven, Michael D.
Cianci, Gianguido C.
McCoombe, Scott G.ORCID iD for McCoombe, Scott G. orcid.org/0000-0001-6717-7511
Kelley, Z. L.
Gioia, Casey J.
Fought, Angela J.
Rademaker, Alfred W.
Veazey, Ronald S.
Hope, Thomas J.
Journal name PLoS pathogens
Volume number 11
Issue number 3
Article ID e1004729
Start page 1
End page 20
Total pages 20
Publisher Public Library of Science
Place of publication San Francisco, Calif.
Publication date 2015-03
ISSN 1553-7374
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
SIMIAN IMMUNODEFICIENCY VIRUS
MALE CIRCUMCISION
INTRAVAGINAL INOCULATION
UNCIRCUMCISED MEN
LANGERHANS CELLS
CERVICAL TISSUE
TARGET-CELLS
INFECTION
PREVENTION
TRIAL
Summary 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.
Language eng
DOI 10.1371/journal.ppat.1004729
Field of Research 110799 Immunology not elsewhere classified
Socio Economic Objective 920109 Infectious Diseases
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30073318

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.