scholarly journals Human Metapneumovirus Small Hydrophobic Protein Inhibits Interferon Induction in Plasmacytoid Dendritic Cells

Viruses ◽  
2018 ◽  
Vol 10 (6) ◽  
pp. 278 ◽  
Author(s):  
Xiaoyong Bao ◽  
Deepthi Kolli ◽  
Dana Esham ◽  
Thangam Velayutham ◽  
Antonella Casola
Keyword(s):  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Human Metapneumovirus ◽  
Hydrophobic Protein ◽  
Interferon Induction ◽  
Small Hydrophobic Protein ◽  
Small Hydrophobic

scholarly journals Small Hydrophobic Protein of Human Metapneumovirus Does Not Affect Virus Replication and Host Gene Expression In Vitro

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e58572 ◽  
Author(s):  
Miranda de Graaf ◽  
Sander Herfst ◽  
Jamil Aarbiou ◽  
Peter C. Burgers ◽  
Fatiha Zaaraoui-Boutahar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virus Replication ◽  
Human Metapneumovirus ◽  
Host Gene ◽  
Host Gene Expression ◽  
Hydrophobic Protein ◽  
Small Hydrophobic Protein ◽  
Small Hydrophobic

scholarly journals Human metapneumovirus activates NOD-like receptor protein 3 inflammasome via its small hydrophobic protein which plays a detrimental role during infection in mice

2019 ◽  
Vol 15 (4) ◽  
pp. e1007689 ◽  
Author(s):  
Vuong B. Lê ◽  
Julia Dubois ◽  
Christian Couture ◽  
Marie-Hélène Cavanagh ◽  
Olus Uyar ◽  
...  
Keyword(s):  
Human Metapneumovirus ◽  
Receptor Protein ◽  
Hydrophobic Protein ◽  
Small Hydrophobic Protein ◽  
Small Hydrophobic

Topology and cellular localization of the small hydrophobic protein of avian metapneumovirus

2011 ◽  
Vol 160 (1-2) ◽  
pp. 102-107 ◽  
Author(s):  
Qiji Deng ◽  
Yuejin Weng ◽  
Wuxun Lu ◽  
Andrew Demers ◽  
Minxun Song ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Avian Metapneumovirus ◽  
Hydrophobic Protein ◽  
Small Hydrophobic Protein ◽  
Small Hydrophobic

scholarly journals Human Metapneumovirus M2-2 Protein Acts as a Negative Regulator of Alpha Interferon Production by Plasmacytoid Dendritic Cells

2017 ◽  
Vol 91 (20) ◽  
Author(s):  
Yoshinori Kitagawa ◽  
Madoka Sakai ◽  
Mariko Funayama ◽  
Masae Itoh ◽  
Bin Gotoh
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis Factor Receptor ◽  
Resonance Energy ◽  
Underlying Mechanism ◽  
Plasmacytoid Dendritic Cells ◽  
Human Metapneumovirus ◽  
Negative Regulator ◽  
Alpha Interferon ◽  
Inhibition Mechanism ◽  
Content Type

ABSTRACT Human metapneumovirus (HMPV) has the ability to inhibit Toll-like receptor 7 (TLR7)- and TLR9-dependent alpha interferon (IFN-α) production by plasmacytoid dendritic cells (pDCs). However, the inhibition mechanism remains largely unknown. To identify viral proteins responsible for this inhibition, we performed a screening of HMPV open reading frames (ORFs) for the ability to block TLR7/9-dependent signaling reconstituted in HEK293T cells by transfection with myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), IKKα, and IFN regulatory factor 7 (IRF7). This screening demonstrated that the M2-2 protein was the most potent inhibitor of TLR7/9-dependent IFN-α induction. A recombinant HMPV in which the M2-2 ORF was silenced indeed induced greater IFN-α production by human pDCs than wild-type HMPV did. Immunoprecipitation experiments showed direct physical association of the M2-2 protein with the inhibitory domain (ID) of IRF7. As a natural consequence of this, transfection of IRF7 lacking the ID, a constitutively active mutant, resulted in activation of the IFN-α promoter even in the presence of M2-2. Bioluminescence resonance energy transfer assays and split Renilla luciferase complementation assays revealed that M2-2 inhibited MyD88/TRAF6/IKKα-induced homodimerization of IRF7. In contrast, expression of the M2-2 protein did not result in inhibition of IPS-1-induced homodimerization and resultant activation of IRF7. This indicates that inhibition of MyD88/TRAF6/IKKα-induced IRF7 homodimerization does not result from a steric effect of M2-2 binding. Instead, it was found that M2-2 inhibited MyD88/TRAF6/IKKα-induced phosphorylation of IRF7 on Ser477. These results suggest that M2-2 blocks TLR7/9-dependent IFN-α induction by preventing IRF7 homodimerization, possibly through its effects on the phosphorylation status of IRF7. IMPORTANCE The family Paramyxoviridae is divided into two subfamilies, the Paramyxovirinae and the Pneumovirinae. Members of the subfamily Paramyxovirinae have the ability to inhibit TLR7/9-dependent IFN-α production, and the underlying inhibition mechanism has been intensively studied. In contrast, little is known about how members of the subfamily Pneumovirinae regulate IFN-α production by pDCs. We identified the M2-2 protein of HMPV, a member of the subfamily Pneumovirinae, as a negative regulator of IFN-α production by pDCs and uncovered the underlying mechanism. This study explains in part why the M2-2 knockout recombinant HMPV is attenuated and further suggests that M2-2 is a potential target for HMPV therapy.

scholarly journals Mumps virus small hydrophobic protein targets ataxin-1 ubiquitin-like interacting protein (ubiquilin 4)

2010 ◽  
Vol 91 (11) ◽  
pp. 2773-2781 ◽  
Author(s):  
M. Woznik ◽  
C. Rodner ◽  
K. Lemon ◽  
B. Rima ◽  
A. Mankertz ◽  
...  
Keyword(s):  
Mumps Virus ◽  
Interacting Protein ◽  
Protein Targets ◽  
Hydrophobic Protein ◽  
Small Hydrophobic Protein ◽  
Small Hydrophobic

scholarly journals Human Metapneumovirus Small Hydrophobic Protein Inhibits NF-κB Transcriptional Activity

2008 ◽  
Vol 82 (16) ◽  
pp. 8224-8229 ◽  
Author(s):  
Xiaoyong Bao ◽  
Deepthi Kolli ◽  
Tianshuang Liu ◽  
Yichu Shan ◽  
Roberto P. Garofalo ◽  
...  
Keyword(s):  
Respiratory Tract Infections ◽  
Nuclear Translocation ◽  
Airway Epithelial Cells ◽  
Human Metapneumovirus ◽  
Airway Epithelial ◽  
Proinflammatory Mediators ◽  
Enhanced Secretion ◽  
Small Hydrophobic Protein ◽  
Tract Infections ◽  
Small Hydrophobic

ABSTRACT Human metapneumovirus, a leading cause of respiratory tract infections in infants, encodes a small hydrophobic (SH) protein of unknown function. In this study, we showed that infection of airway epithelial cells or mice with recombinant human metapneumovirus lacking SH expression (rhMPV-ΔSH) enhanced secretion of proinflammatory mediators, including interleukin 6 (IL-6) and IL-8, encoded by two NF-kB-dependent genes, compared to infection with wild-type rhMPV. RhMPV-ΔSH infection resulted in enhanced NF-kB-dependent gene transcription and in increased levels of phosphorylated and acetylated NF-kB without affecting its nuclear translocation, identifying a possible novel mechanism by which paramyxovirus SH proteins modulate NF-kB activation.

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