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- Girard, L, et al.
(författare)
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Impact of the griffithsin anti-HIV microbicide and placebo gels on the rectal mucosal proteome and microbiome in non-human primates
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 8059-
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Tidskriftsartikel (refereegranskat)abstract
- Topical microbicides are being explored as an HIV prevention method for individuals who practice receptive anal intercourse. In vivo studies of these microbicides are critical to confirm safety. Here, we evaluated the impact of a rectal microbicide containing the antiviral lectin, Griffithsin (GRFT), on the rectal mucosal proteome and microbiome. Using a randomized, crossover placebo-controlled design, six rhesus macaques received applications of hydroxyethylcellulose (HEC)- or carbopol-formulated 0.1% GRFT gels. Rectal mucosal samples were then evaluated by label-free tandem MS/MS and 16 S rRNA gene amplicon sequencing, for proteomics and microbiome analyses, respectively. Compared to placebo, GRFT gels were not associated with any significant changes to protein levels at any time point (FDR < 5%), but increased abundances of two common and beneficial microbial taxa after 24 hours were observed in HEC-GRFT gel (p < 2E-09). Compared to baseline, both placebo formulations were associated with alterations to proteins involved in proteolysis, activation of the immune response and inflammation after 2 hours (p < 0.0001), and increases in beneficial Faecalibacterium spp. after 24 hours in HEC placebo gel (p = 4.21E-15). This study supports the safety profile of 0.1% GRFT gel as an anti-HIV microbicide and demonstrates that current placebo formulations may associate with changes to rectal proteome and microbiota.
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| 6. |
- Klatt, NR, et al.
(författare)
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Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women
- 2017
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 356:6341, s. 938-944
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of HIV clinical trials shows that the vaginal microbiome underlies varied responses to microbicide-based preexposure prophylaxis.
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| 10. |
- Berard, AR, et al.
(författare)
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Mass spectrometry analysis of gut tissue in acute SIV-infection in rhesus macaques identifies early proteome alterations preceding the interferon inflammatory response
- 2022
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Ingår i: SCIENTIFIC REPORTS. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- HIV infection damages the gut mucosa leading to chronic immune activation, increased morbidities and mortality, and antiretroviral therapies, do not completely ameliorate mucosal dysfunction. Understanding early molecular changes in acute infection may identify new biomarkers underlying gut dysfunction. Here we utilized a proteomics approach, coupled with flow cytometry, to characterize early molecular and immunological alterations during acute SIV infection in gut tissue of rhesus macaques. Gut tissue biopsies were obtained at 2 times pre-infection and 4 times post-infection from 6 macaques. The tissue proteome was analyzed by mass spectrometry, and immune cell populations in tissue and blood by flow cytometry. Significant proteome changes (p < 0.05) occurred at 3 days post-infection (dpi) (13.0%), 14 dpi (13.7%), 28 dpi (16.9%) and 63 dpi (14.8%). At 3 dpi, proteome changes included cellular structural activity, barrier integrity, and activation of epithelial to mesenchymal transition (EMT) (FDR < 0.0001) prior to the antiviral response at 14 dpi (IFNa/g pathways, p < 0.001). Novel EMT proteomic biomarkers (keratins 2, 6A and 20, collagen 12A1, desmoplakin) and inflammatory biomarkers (PSMB9, FGL2) were associated with early infection and barrier dysfunction. These findings identify new biomarkers preceding inflammation in SIV infection involved with EMT activation. This warrants further investigation of the role of these biomarkers in chronic infection, mucosal inflammation, and disease pathogenesis of HIV.
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