Tracking the luminal exposure and lymphatic drainage pathways of intravaginal and intrarectal inocula used in nonhuman primate models of HIV transmission

Jeremy Smedley, Baris Turkbey, Marcelino L. Bernardo, Gregory Q. Del Prete, Jacob Estes, Gary L. Griffiths, Hisataka Kobayashi, Peter L. Choyke, Jeffrey D. Lifson, Brandon F. Keele

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Over 80% of sexual HIV-1 transmissions originate from a single viral variant, but the underlying basis for this transmission bottleneck remains to be elucidated. Nonhuman primate models of mucosal virus transmission allow opportunities to gain insight into the basis of this mucosal bottleneck. We used simulated inocula consisting of either non-infectious vital dye or contrast dye with non-invasive magnetic resonance imaging (MRI) to visualize mucosal exposure and passive lymphatic drainage patterns following vaginal and rectal exposures in Indian origin rhesus macaques. Results revealed a limited overall distance of dye coverage from the anal verge following 1 ml (n = 8) intrarectally administered, which greatly increased with a 3 ml (n = 8) volume. Intravaginal dye exposure using 2 ml revealed complete coverage of the mucosa of the vagina and ectocervix, however dye was not detectable in the endocervix, uterus, fallopian tubes or ovaries in nuliparous sexually mature rhesus macaques (n = 9). In addition, following submucosal and intranodal injections of vital dye or MRI contrast dye in the rectum (n = 9), or distal and proximal vagina (n = 4), the lymphatic drainage pathways were identified as first the internal then common iliac chain followed by para-aortic lymph nodes. Drainage from the distal descending colon (n = 8) was via the para-colonic lymph nodes followed by the inferior mesenteric and para-aortic lymph nodes. Analysis after vaginal challenge with infectious SIVmac239 followed by euthanasia at day 3 revealed a pattern of viral dissemination consistent with the imaging results. These results provide insights into potential patterns of viral dissemination that can help guide efforts to better elucidate the earliest events of virus transmission and potential intervention strategies.

Original languageEnglish (US)
Article numbere92830
JournalPLoS One
Volume9
Issue number3
DOIs
StatePublished - Mar 25 2014
Externally publishedYes

Fingerprint

Primates
Drainage
dyes
inoculum
drainage
Coloring Agents
animal models
HIV
lymph nodes
application coverage
Lymph Nodes
virus transmission
vagina
Vagina
Magnetic resonance
Macaca mulatta
Viruses
Imaging techniques
magnetic resonance imaging
Magnetic Resonance Imaging

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Tracking the luminal exposure and lymphatic drainage pathways of intravaginal and intrarectal inocula used in nonhuman primate models of HIV transmission. / Smedley, Jeremy; Turkbey, Baris; Bernardo, Marcelino L.; Del Prete, Gregory Q.; Estes, Jacob; Griffiths, Gary L.; Kobayashi, Hisataka; Choyke, Peter L.; Lifson, Jeffrey D.; Keele, Brandon F.

In: PLoS One, Vol. 9, No. 3, e92830, 25.03.2014.

Research output: Contribution to journalArticle

Smedley, Jeremy ; Turkbey, Baris ; Bernardo, Marcelino L. ; Del Prete, Gregory Q. ; Estes, Jacob ; Griffiths, Gary L. ; Kobayashi, Hisataka ; Choyke, Peter L. ; Lifson, Jeffrey D. ; Keele, Brandon F. / Tracking the luminal exposure and lymphatic drainage pathways of intravaginal and intrarectal inocula used in nonhuman primate models of HIV transmission. In: PLoS One. 2014 ; Vol. 9, No. 3.
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