Article (Scientific journals)
The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission.
Santos da Silva, Eveline; Mulinge, Martin; Lemaire, Morgane et al.
2016In PLoS ONE
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Keywords :
HIV; gp41CT; Env; CD4
Abstract :
[en] The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Santos da Silva, Eveline 
Mulinge, Martin 
Lemaire, Morgane;  Luxembourg Institute of Health > Infection and Immunity > Technician
Masquelier, Cécile;  Luxembourg Institute of Health > Infection and Immunity
Beraud, Cyprien ;  Université de Liège - ULiège > Doct. sc. (bioch., biol. mol.&cell., bioinf.&mod.-Bologne)
Rybicki, Arkadiusz
Servais, Jean-Yves
Iserentant, Gilles
Schmit, Jean-Claude
Seguin-Devaux, Carole
Perez Bercoff, Danielle;  Luxembourg Institute of Health > Infection and Immunity > PI
 These authors have contributed equally to this work.
Language :
English
Title :
The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission.
Publication date :
06 September 2016
Journal title :
PLoS ONE
eISSN :
1932-6203
Publisher :
Public Library of Science, San Franscisco, United States - California
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Luxembourg Ministry of Research and Education MESR Grant# REC-LRTV20101106
Fonds National de la Recherche AFR grant# PHD-09-115 ESS
Fonds National de la Recherche AFR grant# AFR-6012272 CB
Fonds National de la Recherche AFR grant# PHD-08-074 MM
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