Imperial College London
Alternate

ProfessorGeorgiosKassiotis

Faculty of Medicine, Department of Infectious Disease

Professor of Retrovirology
 
 
 
//

Contact

 

g.kassiotis Website

 
 
//

Location

 

Norfolk PlaceSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Eksmond:2017:10.1128/JVI.01152-17,
author = {Eksmond, U and Jenkins, B and Merkenschlager, J and Mothes, W and Stoye, JP and Kassiotis, G},
doi = {10.1128/JVI.01152-17},
journal = {Journal of Virology},
title = {Mutation of the putative immunosuppressive domain of the retroviral envelope glycoprotein compromises infectivity},
url = {http://dx.doi.org/10.1128/JVI.01152-17},
volume = {91},
year = {2017}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The envelope glycoprotein of diverse endogenous and exogenous retroviruses is considered inherently immunosuppressive. Extensive work mapped the immunosuppressive activity to a highly conserved domain, termed the immunosuppressive domain (ISD), in the transmembrane (TM) subunit of the envelope glycoprotein and identified two naturally polymorphic key residues that afford immunosuppressive activity to distinct envelope glycoproteins. Concurrent mutation of these two key residues (E14R and A20F) in the envelope glycoprotein of the Friend murine leukemia virus (F-MLV) ISD has been reported to abolish its immunosuppressive activity, without affecting its fusogenicity, and to weaken the ability of the virus to replicate specifically in immunocompetent hosts. Here, we show that mutation of these key residues did, in fact, result in a substantial loss of F-MLV infectivity, independently of host immunity, challenging whether associations exist between the two. Notably, a loss of infectivity incurred by the F-MLV mutant with the E14R and A20F double ISD mutation was conditional on expression of the ecotropic envelope receptor murine cationic amino acid transporter-1 (mCAT1) in the virus-producing cell. Indeed, the F-MLV mutant retained infectivity when it was produced by human cells, which naturally lack mCAT1 expression, but not by murine cells. Furthermore, mCAT1 overexpression in human cells impaired the infectivity of both the F-MLV double mutant and the wild-type F-MLV strain, suggesting a finely tuned relationship between the levels of mCAT1 in the producer cell and the infectivity of the virions produced. An adverse effect on this relationship, rather than disruption of the putative ISD, is therefore more likely to explain the loss of F-MLV infectivity incurred by mutations in key ISD residues E14 and A20.
AU  - Eksmond,U
AU  - Jenkins,B
AU  - Merkenschlager,J
AU  - Mothes,W
AU  - Stoye,JP
AU  - Kassiotis,G
DO  - 10.1128/JVI.01152-17
PY  - 2017///
SN  - 1098-5514
TI  - Mutation of the putative immunosuppressive domain of the retroviral envelope glycoprotein compromises infectivity
T2  - Journal of Virology
UR  - http://dx.doi.org/10.1128/JVI.01152-17
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000413195400035&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/61404
VL  - 91
ER  -
Download