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{Krebs:2016:10.1186/s12981-016-0125-8,
author = {Krebs, KC and Tian, M and Asmal, M and Ling, B and Nelson, K and Henry, K and Gibson, R and Li, Y and Han, W and Shattock, RJ and Veazey, RS and Letvin, N and Arts, EJ and Gao, Y},
doi = {10.1186/s12981-016-0125-8},
journal = {AIDS Research and Therapy},
title = {Infection of rhesus macaques with a pool of simian immunodeficiency virus with the envelope genes from acute HIV-1 infections},
url = {http://dx.doi.org/10.1186/s12981-016-0125-8},
volume = {13},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background:New simian–human immunodeficiency chimeric viruses with an HIV-1 env (SHIVenv) are critical for studies on HIV pathogenesis, vaccine development, and microbicide testing. Macaques are typically exposed to single CCR5-using SHIVenv which in most instances does not reflect the conditions during acute/early HIV infection (AHI) in humans. Instead of individual and serial testing new SHIV constructs, a pool of SHIVenv_B derived from 16 acute HIV-1 infections were constructed using a novel yeast-based SHIV cloning approach and then used to infect macaques.Results:Even though none of the 16 SHIVenvs contained the recently reported mutations in env genes that could significantly enhance their binding affinity to RhCD4, one SHIVenv (i.e. SHIVenv_B3-PRB926) established infection in macaques exposed to this pool. AHI SHIVenv_B viruses as well as their HIVenv_B counterparts were analyzed for viral protein content, function, and fitness to identify possible difference between SHIVenv_B3-PRB926 and the other 15 SHIVenvs in the pool. All of the constructs produced SHIV or HIV chimeric with wild type levels of capsid (p27 and p24) content, reverse transcriptase (RT) activity, and expressed envelope glycoproteins that could bind to cell receptors CD4/CCR5 and mediate virus entry. HIV-1env_B chimeric viruses were propagated in susceptible cell lines but the 16 SHIVenv_B variants showed only limited replication in macaque peripheral blood mononuclear cells (PBMCs) and 174×CEM.CCR5 cell line. AHI chimeric viruses including HIVenv_B3 showed only minor variations in cell entry efficiency and kinetics as well as replicative fitness in human PBMCs. Reduced number of N-link glycosylation sites and slightly greater CCR5 affinity/avidity was the only distinguishing feature of env_B3 versus other AHI env’s in the pool, a feature also observed in the HIV establishing new infections in humans.Conclusion:Despite the inability to propagate in primary cells and cell lin
AU - Krebs,KC
AU - Tian,M
AU - Asmal,M
AU - Ling,B
AU - Nelson,K
AU - Henry,K
AU - Gibson,R
AU - Li,Y
AU - Han,W
AU - Shattock,RJ
AU - Veazey,RS
AU - Letvin,N
AU - Arts,EJ
AU - Gao,Y
DO - 10.1186/s12981-016-0125-8
PY - 2016///
SN - 1742-6405
TI - Infection of rhesus macaques with a pool of simian immunodeficiency virus with the envelope genes from acute HIV-1 infections
T2 - AIDS Research and Therapy
UR - http://dx.doi.org/10.1186/s12981-016-0125-8
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000388518400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/44005
VL - 13
ER -