NDLI: Oligomerization and GTP-binding Requirements of MxA for Viral Target Recognition and Antiviral Activity against Influenza A Virus.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nigg, Patricia E. Pavlovic, Jovan
Description	Author Affiliation: Nigg PE ( From the Institute of Medical Virology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.); Pavlovic J ( From the Institute of Medical Virology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland pavlovic.jovan@virology.uzh.ch.)
Abstract	The IFN-induced human myxovirus resistance protein A (MxA) exhibits a broad antiviral activity against many viruses, including influenza A virus (IAV). MxA belongs to the family of dynamin-like GTPases and assembles in vitro into dimers, tetramers, and oligomeric ring-like structures. The molecular mechanism of action remains to be elucidated. Furthermore, it is not clear whether MxA exerts its antiviral activity in a monomeric and/or multimeric form. Using a set of MxA mutants that form complexes with defined stoichiometry, we observed that, in the presence of guanosine 5'-O-(thiotriphosphate), purified MxA disassembled into tetramers and dimers. Dimeric forms did not further disassemble into monomers. Infection experiments revealed that besides wild-type MxA, dimeric and monomeric variants of MxA also efficiently restricted IAV at a replication step after primary transcription. Moreover, only dimeric MxA was able to form stable complexes with the nucleoprotein (NP) of IAV. MxA interacted with NP independently of other viral components. Interestingly, the dimeric form of MxA was able to efficiently bind to NP from several MxA-sensitive strains but interacted much more weakly with NP from the MxA-resistant PR8 strain derived from the H1N1 1918 lineage. Taken together, these data suggest that, during infection, a fraction of MxA disassembles into dimers that bind to NP synthesized following primary transcription in the cytoplasm, thereby preventing viral replication.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	50
Volume Number	290
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2015-12-11
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Biopolymers Metabolism Guanosine Triphosphate Influenza A Virus Myxovirus Resistance Proteins Animals Cell Line Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in