Cargando…

Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa

Whilst short-term oral pre-exposure prophylaxis (PrEP) with antiretroviral drugs in men who have sex with men has shown protection against HIV-1 infection, the impact of this regimen on the in vivo foreskin transcriptome is unknown. We collected foreskin tissue after voluntary medical male circumcis...

Descripción completa

Detalles Bibliográficos
Autores principales: Petkov, Stefan, Herrera, Carolina, Else, Laura, Lebina, Limakatso, Opoka, Daniel, Seiphetlo, Thabiso B., Pillay, Azure-Dee AP., Mugaba, Susan, Namubiru, Patricia, Odoch, Geoffrey, Ssemata, Andrew S., Serwanga, Jennifer, Kaleebu, Pontiano, Webb, Emily L., Khoo, Saye, Martinson, Neil, Gray, Clive M., Fox, Julie, Chiodi, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9720390/
https://www.ncbi.nlm.nih.gov/pubmed/36479111
http://dx.doi.org/10.3389/fimmu.2022.1009978
_version_ 1784843546895843328
author Petkov, Stefan
Herrera, Carolina
Else, Laura
Lebina, Limakatso
Opoka, Daniel
Seiphetlo, Thabiso B.
Pillay, Azure-Dee AP.
Mugaba, Susan
Namubiru, Patricia
Odoch, Geoffrey
Ssemata, Andrew S.
Serwanga, Jennifer
Kaleebu, Pontiano
Webb, Emily L.
Khoo, Saye
Martinson, Neil
Gray, Clive M.
Fox, Julie
Chiodi, Francesca
author_facet Petkov, Stefan
Herrera, Carolina
Else, Laura
Lebina, Limakatso
Opoka, Daniel
Seiphetlo, Thabiso B.
Pillay, Azure-Dee AP.
Mugaba, Susan
Namubiru, Patricia
Odoch, Geoffrey
Ssemata, Andrew S.
Serwanga, Jennifer
Kaleebu, Pontiano
Webb, Emily L.
Khoo, Saye
Martinson, Neil
Gray, Clive M.
Fox, Julie
Chiodi, Francesca
author_sort Petkov, Stefan
collection PubMed
description Whilst short-term oral pre-exposure prophylaxis (PrEP) with antiretroviral drugs in men who have sex with men has shown protection against HIV-1 infection, the impact of this regimen on the in vivo foreskin transcriptome is unknown. We collected foreskin tissue after voluntary medical male circumcision from 144 young men (72 from Uganda and 72 from South Africa) randomized to one to two doses of either oral tenofovir (TFV) disoproxil fumarate (FTC-TDF) or tenofovir alafenamide (FTC-TAF) or no drug (untreated controls). This novel approach allowed us to examine the impact of short-term oral PrEP on transcriptome of the male genital tract. A single dose of FTC-TDF did not affect the foreskin transcriptome in relation to control arm, however one dose of FTC-TAF induced upregulation of four genes AKAP8, KIAA0141, HSCB and METTL17. Following two doses of either FTC-TDF or FTC-TAF, there was an increase in 34 differentially expressed genes for FTC-TDF and 15 for FTC-TAF, with nine DEGs in common: KIAA0141, SAFB2, CACTIN, FXR2, AKAP8, HSCB, CLNS1A, DDX27 and DCAF15. Functional analysis of differentially expressed genes revealed modulation of biological processes related to mitochondrial stress (KIAA0141, HSCB and METTL17), anti-viral and anti-inflammatory pathways (CACTIN and AKAP8). Our results show that short-course on-demand oral PrEP in men modulates genes in foreskin tissue which are likely unfavorable to HIV acquisition and replication. We also describe an upregulated expression of genes involved in diverse mitochondria biology which may potentially result in worsened mitochondria-related. These results warrant further studies to assess the role of short-course and prolonged oral PrEP on biological processes of the foreskin mucosa.
format Online
Article
Text
id pubmed-9720390
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-97203902022-12-06 Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa Petkov, Stefan Herrera, Carolina Else, Laura Lebina, Limakatso Opoka, Daniel Seiphetlo, Thabiso B. Pillay, Azure-Dee AP. Mugaba, Susan Namubiru, Patricia Odoch, Geoffrey Ssemata, Andrew S. Serwanga, Jennifer Kaleebu, Pontiano Webb, Emily L. Khoo, Saye Martinson, Neil Gray, Clive M. Fox, Julie Chiodi, Francesca Front Immunol Immunology Whilst short-term oral pre-exposure prophylaxis (PrEP) with antiretroviral drugs in men who have sex with men has shown protection against HIV-1 infection, the impact of this regimen on the in vivo foreskin transcriptome is unknown. We collected foreskin tissue after voluntary medical male circumcision from 144 young men (72 from Uganda and 72 from South Africa) randomized to one to two doses of either oral tenofovir (TFV) disoproxil fumarate (FTC-TDF) or tenofovir alafenamide (FTC-TAF) or no drug (untreated controls). This novel approach allowed us to examine the impact of short-term oral PrEP on transcriptome of the male genital tract. A single dose of FTC-TDF did not affect the foreskin transcriptome in relation to control arm, however one dose of FTC-TAF induced upregulation of four genes AKAP8, KIAA0141, HSCB and METTL17. Following two doses of either FTC-TDF or FTC-TAF, there was an increase in 34 differentially expressed genes for FTC-TDF and 15 for FTC-TAF, with nine DEGs in common: KIAA0141, SAFB2, CACTIN, FXR2, AKAP8, HSCB, CLNS1A, DDX27 and DCAF15. Functional analysis of differentially expressed genes revealed modulation of biological processes related to mitochondrial stress (KIAA0141, HSCB and METTL17), anti-viral and anti-inflammatory pathways (CACTIN and AKAP8). Our results show that short-course on-demand oral PrEP in men modulates genes in foreskin tissue which are likely unfavorable to HIV acquisition and replication. We also describe an upregulated expression of genes involved in diverse mitochondria biology which may potentially result in worsened mitochondria-related. These results warrant further studies to assess the role of short-course and prolonged oral PrEP on biological processes of the foreskin mucosa. Frontiers Media S.A. 2022-11-18 /pmc/articles/PMC9720390/ /pubmed/36479111 http://dx.doi.org/10.3389/fimmu.2022.1009978 Text en Copyright © 2022 Petkov, Herrera, Else, Lebina, Opoka, Seiphetlo, Pillay, Mugaba, Namubiru, Odoch, Ssemata, Serwanga, Kaleebu, Webb, Khoo, Martinson, Gray, Fox and Chiodi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Petkov, Stefan
Herrera, Carolina
Else, Laura
Lebina, Limakatso
Opoka, Daniel
Seiphetlo, Thabiso B.
Pillay, Azure-Dee AP.
Mugaba, Susan
Namubiru, Patricia
Odoch, Geoffrey
Ssemata, Andrew S.
Serwanga, Jennifer
Kaleebu, Pontiano
Webb, Emily L.
Khoo, Saye
Martinson, Neil
Gray, Clive M.
Fox, Julie
Chiodi, Francesca
Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa
title Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa
title_full Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa
title_fullStr Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa
title_full_unstemmed Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa
title_short Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa
title_sort short-term oral pre-exposure prophylaxis against hiv-1 modulates the transcriptome of foreskin tissue in young men in africa
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9720390/
https://www.ncbi.nlm.nih.gov/pubmed/36479111
http://dx.doi.org/10.3389/fimmu.2022.1009978
work_keys_str_mv AT petkovstefan shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT herreracarolina shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT elselaura shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT lebinalimakatso shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT opokadaniel shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT seiphetlothabisob shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT pillayazuredeeap shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT mugabasusan shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT namubirupatricia shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT odochgeoffrey shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT ssemataandrews shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT serwangajennifer shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT kaleebupontiano shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT webbemilyl shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT khoosaye shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT martinsonneil shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT grayclivem shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT foxjulie shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica
AT chiodifrancesca shorttermoralpreexposureprophylaxisagainsthiv1modulatesthetranscriptomeofforeskintissueinyoungmeninafrica