Next Article in Journal
Roles of the Fc Receptor γ-Chain in Inducing Protective Immune Responses after Heterologous Vaccination against Respiratory Syncytial Virus Infection
Next Article in Special Issue
The Importance of Regulation in Natural Immunity to HIV
Previous Article in Journal
Stability of Outer Membrane Vesicles-Based Vaccines, Identifying the Most Appropriate Methods to Detect Changes in Vaccine Potency
Previous Article in Special Issue
HIV-Exposed Seronegative Sex Workers Express Low T-Cell Activation and an Intact Ectocervical Tissue Microenvironment
Article

Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs

1
Centre for Infection & Immunity, Division of Clinical Sciences, St George’s University of London, London SW17 0RE, UK
2
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
3
Division of Clinical Sciences, St George’s University of London, London SW17 0RE, UK
*
Author to whom correspondence should be addressed.
Current address: Department of Medicine, Imperial College London, London W2 1PG, UK.
Current address: School of Biological and Chemical Sciences, Queen Mary University of London, Bethnal Green, London E1 4NS, UK.
Academic Editor: Johanne Poudrier
Vaccines 2021, 9(3), 231; https://doi.org/10.3390/vaccines9030231
Received: 31 January 2021 / Revised: 26 February 2021 / Accepted: 26 February 2021 / Published: 8 March 2021
(This article belongs to the Special Issue Mucosal Responses in the Context of Natural Immunity to HIV)
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. View Full-Text
Keywords: HIV-1; mucosal tissue; antiretrovirals; pre-exposure prophylaxis HIV-1; mucosal tissue; antiretrovirals; pre-exposure prophylaxis
Show Figures

Figure 1

MDPI and ACS Style

Herrera, C.; McRaven, M.D.; Laing, K.G.; Dennis, J.; Hope, T.J.; Shattock, R.J. Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs. Vaccines 2021, 9, 231. https://doi.org/10.3390/vaccines9030231

AMA Style

Herrera C, McRaven MD, Laing KG, Dennis J, Hope TJ, Shattock RJ. Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs. Vaccines. 2021; 9(3):231. https://doi.org/10.3390/vaccines9030231

Chicago/Turabian Style

Herrera, Carolina, Mike D. McRaven, Ken G. Laing, Jayne Dennis, Thomas J. Hope, and Robin J. Shattock 2021. "Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs" Vaccines 9, no. 3: 231. https://doi.org/10.3390/vaccines9030231

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop