Imperial College London

ProfessorRobinShattock

Faculty of MedicineDepartment of Infectious Disease

Chair in Mucosal Infection and Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5206r.shattock

 
 
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Location

 

453Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Fletcher:2005:10.1128/JVI.79.17.11179-11186.2005,
author = {Fletcher, P and Kiselyeva, Y and Wallace, G and Romano, J and Griffin, G and Margolis, L and Shattock, R},
doi = {10.1128/JVI.79.17.11179-11186.2005},
journal = {J Virol},
pages = {11179--11186},
title = {The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human immunodeficiency virus type 1 infection of human cervical tissue and dissemination by migratory cells.},
url = {http://dx.doi.org/10.1128/JVI.79.17.11179-11186.2005},
volume = {79},
year = {2005}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Heterosexual transmission of human immunodeficiency virus remains the major route of transmission worldwide; thus, there is an urgent need for additional prevention strategies, particularly those that could be controlled by women. Using cellular and tissue explant models, we have evaluated the potential activity of thiocarboxanilide nonnucleoside analogue reverse transcriptase inhibitor UC-781 as a vaginal microbicide. We were able to demonstrate a potent dose-dependent effect against R5 and X4 infections of T cells. In human cervical explant cultures, UC-781 was not only able to inhibit direct infection of mucosal tissue but was able to prevent dissemination of virus by migratory cells. UC-781 formulated into a carbopol gel (0.1%) retained significant activity against both direct tissue infection and transinfection mediated by migratory cells. Furthermore, UC-781 demonstrated prolonged inhibitory effects able to prevent both localized and disseminated infections up to 6 days post compound treatment. Additional studies were carried out to determine the concentration of compound that might be required to block a primary infection within draining lymph nodes. While a greater dose of compound was required to inhibit both X4 and R5 infections of lymphoid versus cervical explants, this was equivalent to a 1:3,000 dilution of the 0.1% formulation. Furthermore, a 2-h exposure to the compound prevented infection of lymphoid tissue when challenged up to 2 days later. The prolonged protection observed following pretreatment of both genital and lymphoid tissues with UC-781 suggests that this class of inhibitors may have unique advantages over other classes of potential microbicide candidates.
AU - Fletcher,P
AU - Kiselyeva,Y
AU - Wallace,G
AU - Romano,J
AU - Griffin,G
AU - Margolis,L
AU - Shattock,R
DO - 10.1128/JVI.79.17.11179-11186.2005
EP - 11186
PY - 2005///
SN - 0022-538X
SP - 11179
TI - The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human immunodeficiency virus type 1 infection of human cervical tissue and dissemination by migratory cells.
T2 - J Virol
UR - http://dx.doi.org/10.1128/JVI.79.17.11179-11186.2005
UR - https://www.ncbi.nlm.nih.gov/pubmed/16103169
VL - 79
ER -