Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels.
Human metapneumovirus (hMPV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN) signaling by an unidentified mechanism. In this study, we showed that infection of airway epithelial cells with hMPV decreased cellular level of Janus tyrosine kinase (Jak1) and...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2011-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3176284?pdf=render |
id |
doaj-97d09e67dbdf43448457a0e899addca5 |
---|---|
record_format |
Article |
spelling |
doaj-97d09e67dbdf43448457a0e899addca52020-11-25T01:24:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2449610.1371/journal.pone.0024496Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels.Junping RenDeepthi KolliTianshuang LiuRenling XuRoberto P GarofaloAntonella CasolaXiaoyong BaoHuman metapneumovirus (hMPV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN) signaling by an unidentified mechanism. In this study, we showed that infection of airway epithelial cells with hMPV decreased cellular level of Janus tyrosine kinase (Jak1) and tyrosine kinase 2 (Tyk2), due to enhanced proteosomal degradation and reduced gene transcription. In addition, hMPV infection also reduced the surface expression of type I IFN receptor (IFNAR). These inhibitory mechanisms are different from the ones employed by respiratory syncytial virus (RSV), which does not affect Jak1, Tyk2 or IFNAR expression, but degrades downstream signal transducer and activator of transcription proteins 2 (STAT2), although both viruses are pneumoviruses belonging to the Paramyxoviridae family. Our study identifies a novel mechanism by which hMPV inhibits STAT1 and 2 activation, ultimately leading to viral evasion of host IFN responses.http://europepmc.org/articles/PMC3176284?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Junping Ren Deepthi Kolli Tianshuang Liu Renling Xu Roberto P Garofalo Antonella Casola Xiaoyong Bao |
spellingShingle |
Junping Ren Deepthi Kolli Tianshuang Liu Renling Xu Roberto P Garofalo Antonella Casola Xiaoyong Bao Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels. PLoS ONE |
author_facet |
Junping Ren Deepthi Kolli Tianshuang Liu Renling Xu Roberto P Garofalo Antonella Casola Xiaoyong Bao |
author_sort |
Junping Ren |
title |
Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels. |
title_short |
Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels. |
title_full |
Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels. |
title_fullStr |
Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels. |
title_full_unstemmed |
Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels. |
title_sort |
human metapneumovirus inhibits ifn-β signaling by downregulating jak1 and tyk2 cellular levels. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
Human metapneumovirus (hMPV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN) signaling by an unidentified mechanism. In this study, we showed that infection of airway epithelial cells with hMPV decreased cellular level of Janus tyrosine kinase (Jak1) and tyrosine kinase 2 (Tyk2), due to enhanced proteosomal degradation and reduced gene transcription. In addition, hMPV infection also reduced the surface expression of type I IFN receptor (IFNAR). These inhibitory mechanisms are different from the ones employed by respiratory syncytial virus (RSV), which does not affect Jak1, Tyk2 or IFNAR expression, but degrades downstream signal transducer and activator of transcription proteins 2 (STAT2), although both viruses are pneumoviruses belonging to the Paramyxoviridae family. Our study identifies a novel mechanism by which hMPV inhibits STAT1 and 2 activation, ultimately leading to viral evasion of host IFN responses. |
url |
http://europepmc.org/articles/PMC3176284?pdf=render |
work_keys_str_mv |
AT junpingren humanmetapneumovirusinhibitsifnbsignalingbydownregulatingjak1andtyk2cellularlevels AT deepthikolli humanmetapneumovirusinhibitsifnbsignalingbydownregulatingjak1andtyk2cellularlevels AT tianshuangliu humanmetapneumovirusinhibitsifnbsignalingbydownregulatingjak1andtyk2cellularlevels AT renlingxu humanmetapneumovirusinhibitsifnbsignalingbydownregulatingjak1andtyk2cellularlevels AT robertopgarofalo humanmetapneumovirusinhibitsifnbsignalingbydownregulatingjak1andtyk2cellularlevels AT antonellacasola humanmetapneumovirusinhibitsifnbsignalingbydownregulatingjak1andtyk2cellularlevels AT xiaoyongbao humanmetapneumovirusinhibitsifnbsignalingbydownregulatingjak1andtyk2cellularlevels |
_version_ |
1725119313170399232 |