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{Peters:2015:10.1186/s12977-015-0176-2,
author = {Peters, PJ and Gonzalez-Perez, MP and Musich, T and Simas, TAM and Lin, R and Morse, AN and Shattock, RJ and Derdeyn, CA and Clapham, PR},
doi = {10.1186/s12977-015-0176-2},
journal = {Retrovirology},
title = {Infection of ectocervical tissue and universal targeting of T-cells mediated by primary non-macrophage-tropic and highly macrophage-tropic HIV-1 R5 envelopes},
url = {http://dx.doi.org/10.1186/s12977-015-0176-2},
volume = {12},
year = {2015}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background: HIV-1 variants carrying non-macrophage-tropic HIV-1 R5 envelopes (Envs) are predominantly transmitted and persist in immune tissue even in AIDS patients who have highly macrophage-tropic variants in the brain.Non-macrophage-tropic R5 Envs require high levels of CD4 for infection contrasting with macrophage-tropic Envs,which can efficiently mediate infection of cells via low CD4. Here, we investigated whether non-macrophage-tropicR5 Envs from the acute stage of infection (including transmitted/founder Env) mediated more efficient infection ofectocervical explant cultures compared to non-macrophage-tropic and highly macrophage-tropic R5 Envs from latedisease.Results: We used Env+ pseudovirions that carried a GFP reporter gene to measure infection of the first cells targetedin ectocervical explant cultures. In straight titrations of Env+ pseudovirus supernatants, mac-tropic R5 Envs from latedisease mediated slightly higher infectivities for ectocervical explants although this was not significant. Surprisingly,explant infection by several T/F/acute Envs was lower than for Envs from late disease. However, when infectivity forexplants was corrected to account for differences in the overall infectivity of each Env+ pseudovirus (measured onhighly permissive HeLa TZM-bl cells), non-mac-tropic early and late disease Env+ pseudoviruses mediated significantly higher infection. This observation suggests that cervical tissue preferentially supports non-mac-tropic Env+viruses compared to mac-tropic viruses. Finally, we show that T-cells were the main targets for infection regardless ofwhether explants were stimulated with T-cell or monocyte/macrophage cytokines. There was no evidence of macrophage infection even for pseudovirions carrying highly mac-tropic Envs from brain tissue or for the highly mactropic,laboratory strain, BaL, which targeted T-cells in the explant tissue.Conclusions: Our data support ectocervical tissue as a favorable environment for non-mac-trop
AU - Peters,PJ
AU - Gonzalez-Perez,MP
AU - Musich,T
AU - Simas,TAM
AU - Lin,R
AU - Morse,AN
AU - Shattock,RJ
AU - Derdeyn,CA
AU - Clapham,PR
DO - 10.1186/s12977-015-0176-2
PY - 2015///
SN - 1742-4690
TI - Infection of ectocervical tissue and universal targeting of T-cells mediated by primary non-macrophage-tropic and highly macrophage-tropic HIV-1 R5 envelopes
T2 - Retrovirology
UR - http://dx.doi.org/10.1186/s12977-015-0176-2
UR - http://hdl.handle.net/10044/1/26316
VL - 12
ER -