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Title: Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

Abstract

Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2more » virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive infection.« less

Authors:
 [1];  [2];  [3]
  1. D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation)
  2. School of Biosciences, University of Kent, Canterbury CT27NJ (United Kingdom)
  3. Institute of Virology, Philipps University, Marburg 35037 (Germany)
Publication Date:
OSTI Identifier:
22581688
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 492; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; GLYCOPROTEINS; IN VITRO; INFECTIVITY; INFLUENZA; INFLUENZA VIRUSES; LIPIDS; PH VALUE; RNA; TRYPSIN

Citation Formats

Zhirnov, O.P., E-mail: zhirnov@inbox.ru, Manykin, A. A., Rossman, J. S., and Klenk, H. D. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity. United States: N. p., 2016. Web. doi:10.1016/J.VIROL.2016.02.021.
Zhirnov, O.P., E-mail: zhirnov@inbox.ru, Manykin, A. A., Rossman, J. S., & Klenk, H. D. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity. United States. https://doi.org/10.1016/J.VIROL.2016.02.021
Zhirnov, O.P., E-mail: zhirnov@inbox.ru, Manykin, A. A., Rossman, J. S., and Klenk, H. D. 2016. "Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity". United States. https://doi.org/10.1016/J.VIROL.2016.02.021.
@article{osti_22581688,
title = {Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity},
author = {Zhirnov, O.P., E-mail: zhirnov@inbox.ru and Manykin, A. A. and Rossman, J. S. and Klenk, H. D.},
abstractNote = {Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive infection.},
doi = {10.1016/J.VIROL.2016.02.021},
url = {https://www.osti.gov/biblio/22581688}, journal = {Virology},
issn = {0042-6822},
number = ,
volume = 492,
place = {United States},
year = {Sun May 15 00:00:00 EDT 2016},
month = {Sun May 15 00:00:00 EDT 2016}
}