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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
HTLV-1 evades type I interferon antiviral signaling by inducing the suppressor of cytokine signaling 1 (SOCS1)
PLoS Pathogens, Volume 6, No. 11, Article e1001177, Year 2010
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Description
Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of Adult T cell Leukemia (ATL) and the neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the majority of HTLV-1-infected individuals remain asymptomatic carriers (AC) during their lifetime, 2-5% will develop either ATL or HAM/TSP, but never both. To better understand the gene expression changes in HTLV-1-associated diseases, we examined the mRNA profiles of CD4+ T cells isolated from 7 ATL, 12 HAM/TSP, 11 AC and 8 non-infected controls. Using genomic approaches followed by bioinformatic analysis, we identified gene expression pattern characteristic of HTLV-1 infected individuals and particular disease states. Of particular interest, the suppressor of cytokine signaling 1-SOCS1-was upregulated in HAM/TSP and AC patients but not in ATL. Moreover, SOCS1 was positively correlated with the expression of HTLV-1 mRNA in HAM/TSP patient samples. In primary PBMCs transfected with a HTLV-1 proviral clone and in HTLV-1-transformed MT-2 cells, HTLV-1 replication correlated with induction of SOCS1 and inhibition of IFN-a/b and IFN-stimulated gene expression. Targeting SOCS1 with siRNA restored type I IFN production and reduced HTLV-1 replication in MT-2 cells. Conversely, exogenous expression of SOCS1 resulted in enhanced HTLV-1 mRNA synthesis. In addition to inhibiting signaling downstream of the IFN receptor, SOCS1 inhibited IFN-b production by targeting IRF3 for ubiquitination and proteasomal degradation. These observations identify a novel SOCS1 driven mechanism of evasion of the type I IFN antiviral response against HTLV-1 © 2010 Olière et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2973829/bin/ppat.1001177.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC2973829/bin/ppat.1001177.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC2973829/bin/ppat.1001177.s003.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC2973829/bin/ppat.1001177.s004.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2973829/bin/ppat.1001177.s005.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2973829/bin/ppat.1001177.s006.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2973829/bin/ppat.1001177.s007.xls
Authors & Co-Authors
Olière, Stéphanie
Canada, Montreal
Institut Lady Davis de Recherches Médicales
Canada, Montreal
Université Mcgill
Hernandez, Eduardo
Canada, Montreal
Institut Lady Davis de Recherches Médicales
Lézin, Agnès
France, Pointe-a-pitre
Universite Des Antilles et de la Guyane
Arguello, Meztli
Canada, Montreal
Institut Lady Davis de Recherches Médicales
Douville, Renée
Canada, Montreal
Institut Lady Davis de Recherches Médicales
Canada, Montreal
Université Mcgill
Nguyên, Thi Liên Anh
Canada, Montreal
Institut Lady Davis de Recherches Médicales
Canada, Montreal
Université Mcgill
Olindo, Stéphane
France, Pointe-a-pitre
Universite Des Antilles et de la Guyane
Panelatti, Gérard
France, Pointe-a-pitre
Universite Des Antilles et de la Guyane
Kazanji, Mirdad
Gabon, Franceville
Centre International de Recherches Medicales de Franceville
Wilkinson, Peter A.
Canada, Montreal
Centre Hospitalier de L'universite de Montreal
United States, Port Saint Lucie
Vaccine and Gene Therapy Institute of Florida
Seḱaly, Rafick Pierre
Canada, Montreal
Centre Hospitalier de L'universite de Montreal
United States, Port Saint Lucie
Vaccine and Gene Therapy Institute of Florida
Césaire, Raymond
France, Pointe-a-pitre
Universite Des Antilles et de la Guyane
Hiscott, John B.
Canada, Montreal
Institut Lady Davis de Recherches Médicales
Canada, Montreal
Université Mcgill
Statistics
Citations: 13
Authors: 13
Affiliations: 6
Identifiers
Doi:
10.1371/journal.ppat.1001177
ISSN:
15537366
e-ISSN:
15537374
Research Areas
Genetics And Genomics
Health System And Policy