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Impact of Q-Griffithsin anti-HIV microbicide gel in non-human primates: In situ analyses of epithelial and immune cell markers in rectal mucosa
Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Div Infect Dis, Stockholm, Sweden.
Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Div Infect Dis, Stockholm, Sweden.
CDC, Natl Ctr HIV AIDS Viral Hepatitis Sexually Transm, Div HIV AIDS Prevent, Lab Branch, Atlanta, GA 30333 USA.
Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Med Solna,Div Infect Dis, Stockholm, Sweden.
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 18120Article in journal (Refereed) Published
Abstract [en]

Natural-product derived lectins can function as potent viral inhibitors with minimal toxicity as shown in vitro and in small animal models. We here assessed the effect of rectal application of an anti-HIV lectin-based microbicide Q-Griffithsin (Q-GRFT) in rectal tissue samples from rhesus macaques. E-cadherin(+) cells, CD4(+) cells and total mucosal cells were assessed using in situ staining combined with a novel customized digital image analysis platform. Variations in cell numbers between baseline, placebo and Q-GRFT treated samples were analyzed using random intercept linear mixed effect models. The frequencies of rectal E-cadherin(+) cells remained stable despite multiple tissue samplings and Q-GRFT gel (0.1%, 0.3% and 1%, respectively) treatment. Whereas single dose application of Q-GRFT did not affect the frequencies of rectal CD4(+) cells, multi-dose Q-GRFT caused a small, but significant increase of the frequencies of intra-epithelial CD4(+) cells (placebo: median 4%; 1% Q-GRFT: median 7%) and of the CD4(+) lamina propria cells (placebo: median 30%; 0.1-1% Q-GRFT: median 36-39%). The resting time between sampling points were further associated with minor changes in the total and CD4(+) rectal mucosal cell levels. The results add to general knowledge of in vivo evaluation of anti-HIV microbicide application concerning cellular effects in rectal mucosa.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 9, article id 18120
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Cell and Molecular Biology
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URN: urn:nbn:se:uu:diva-400679DOI: 10.1038/s41598-019-54493-4ISI: 000500566600001PubMedID: 31792342OAI: oai:DiVA.org:uu-400679DiVA, id: diva2:1382181
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Swedish Research CouncilAvailable from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02Bibliographically approved

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