Herrera, C; McRaven, MD; Laing, KG; Dennis, J; Hope, TJ; Shattock, RJ
(2021)
Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs.
Vaccines (Basel), 9 (3).
p. 231.
ISSN 2076-393X
https://doi.org/10.3390/vaccines9030231
SGUL Authors: Laing, Kenneth
Abstract
Innate responses during acute HIV infection correlate with disease progression and pathogenesis. However, limited information is available about the events occurring during the first hours of infection in the mucosal sites of transmission. With an ex vivo HIV-1 challenge model of human colorectal tissue we assessed the mucosal responses induced by R5- and X4-tropic HIV-1 isolates in the first 24 h of exposure. Microscopy studies demonstrated virus penetration of up to 39 μm into the lamina propia within 6 h of inoculation. A rapid, 6 h post-challenge, increase in the level of secretion of inflammatory cytokines, chemokines, interferon- γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed following exposure to R5- or X4-tropic isolates. This profile persisted at the later time point measured of 24 h. However, exposure to the X4-tropic isolate tested induced greater changes at the proteomic and transcriptomic levels than the R5-tropic. The X4-isolate induced greater levels of CCR5 ligands (RANTES, MIP-1α and MIP-1β) secretion than R5-HIV-1. Potential drugs candidates for colorectal microbicides, including entry, fusion or reverse transcriptase inhibitors demonstrated differential capacity to modulate these responses. Our findings indicate that in colorectal tissue, inflammatory responses and a Th1 cytokine profile are induced in the first 24 h following viral exposure.
Item Type: |
Article
|
Additional Information: |
Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
Keywords: |
HIV-1, antiretrovirals, mucosal tissue, pre-exposure prophylaxis, HIV-1, mucosal tissue, antiretrovirals, pre-exposure prophylaxis |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Vaccines (Basel) |
ISSN: |
2076-393X |
Language: |
eng |
Dates: |
Date | Event |
---|
8 March 2021 | Published | 26 February 2021 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
Project ID | Funder | Funder ID |
---|
106756-41-RFMT | amfAR, The Foundation for AIDS Research | UNSPECIFIED | AI060614 | NIH HHS | UNSPECIFIED |
|
PubMed ID: |
33800213 |
Web of Science ID: |
WOS:000634234500001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/113180 |
Publisher's version: |
https://doi.org/10.3390/vaccines9030231 |
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