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Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs
- Source :
- Vaccines, Vol 9, Iss 231, p 231 (2021), Vaccines, Volume 9, Issue 3
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
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.
- Subjects :
- 0301 basic medicine
Chemokine
030106 microbiology
Immunology
lcsh:Medicine
Research & Experimental Medicine
Virus
Article
Proinflammatory cytokine
Pathogenesis
03 medical and health sciences
Interferon
Drug Discovery
Medicine
Pharmacology (medical)
Secretion
antiretrovirals
pre-exposure prophylaxis
Pharmacology
Science & Technology
biology
business.industry
mucosal tissue
lcsh:R
Reverse transcriptase
030104 developmental biology
Infectious Diseases
Medicine, Research & Experimental
biology.protein
HIV-1
business
Life Sciences & Biomedicine
Ex vivo
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 2076393X
- Volume :
- 9
- Issue :
- 231
- Database :
- OpenAIRE
- Journal :
- Vaccines
- Accession number :
- edsair.doi.dedup.....8e90497e21515e3fe3608bc795d57f74