HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Life Science / Faculty of Advanced Life Science >
Peer-reviewed Journal Articles, etc >

The Measles Virus V Protein Binding Site to STAT2 Overlaps That of IRF9

Files in This Item:

The file(s) associated with this item can be obtained from the following URL:

Title: The Measles Virus V Protein Binding Site to STAT2 Overlaps That of IRF9
Authors: Nagano, Yuma Browse this author
Sugiyama, Aoi Browse this author
Kimoto, Madoka Browse this author
Wakahara, Takuya Browse this author
Noguchi, Yasuyo Browse this author
Jiang, Xinxin Browse this author
Saijo, Shinya Browse this author
Shimizu, Nobutaka Browse this author
Yabuno, Nana Browse this author
Yao, Min Browse this author
Gooley, Paul R. Browse this author
Moseley, Gregory W. Browse this author
Tadokoro, Takashi Browse this author
Maenaka, Katsumi Browse this author
Ose, Toyoyuki Browse this author →KAKEN DB
Keywords: STAT transcription factors
immune evasion
innate immunity
protein purification
protein-protein interactions
recombinant-protein production
structural biology
zinc finger proteins
Issue Date: Sep-2020
Publisher: American Society for Microbiology
Journal Title: Journal of Virology
Volume: 94
Issue: 17
Start Page: e01169-20
Publisher DOI: 10.1128/JVI.01169-20
Abstract: Measles virus (MeV) is a highly immunotropic and contagious pathogen that can even diminish preexisting antibodies and remains a major cause of childhood morbidity and mortality worldwide despite the availability of effective vaccines. MeV is one of the most extensively studied viruses with respect to the mechanisms of JAK-STAT antagonism. Of the three proteins translated from the MeV P gene, P and V are essential for inactivation of this pathway. However, the lack of data from direct analyses of the underlying interactions means that the detailed molecular mechanism of antagonism remains unresolved. Here, we prepared recombinant MeV V protein, which is responsible for human JAK-STAT antagonism, and a panel of variants, enabling the biophysical characterization of V protein, including direct V/STAT1 and V/STAT2 interaction assays. Unambiguous direct interactions between the host and viral factors, in the absence of other factors such as Jak1 or Tyk2, were observed, and the dissociation constants were quantified for the first time. Our data indicate that interactions between the C-terminal region of V and STAT2 is 1 order of magnitude stronger than that of the N-terminal region of V and STAT1. We also clarified that these interactions are completely independent of each other. Moreover, results of size exclusion chromatography demonstrated that addition of MeV-V displaces STAT2-core, a rigid region of STAT2 lacking the N- and C-terminal domains, from preformed complexes of STAT2-core/IRF-associated domain (IRF9). These results provide a novel model whereby MeV-V can not only inhibit the STAT2/IRF9 interaction but also disrupt preassembled interferon-stimulated gene factor 3. IMPORTANCE To evade host immunity, many pathogenic viruses inactivate host Janus kinase signal transducer and activator of transcription (STAT) signaling pathways using diverse strategies. Measles virus utilizes P and V proteins to counteract this signaling pathway. Data derived largely from cell-based assays have indicated several amino acid residues of P and V proteins as important. However, biophysical properties of V protein or its direct interaction with STAT molecules using purified proteins have not been studied. We have developed novel molecular tools enabling us to identify a novel molecular mechanism for immune evasion whereby V protein disrupts critical immune complexes, providing a clear strategy by which measles virus can suppress interferon-mediated antiviral gene expression.
Type: article
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 - Hokkaido University