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Journal of Virology, August 2009, p. 7842-7849, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00309-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Nucleoprotein of Lymphocytic Choriomeningitis Virus Facilitates Spread of Persistent Infection through Stabilization of the Keratin Network{triangledown}

Martina Labudova,1 Jana Tomaskova,1 Ludovit Skultety,1,2 Jaromir Pastorek,1 and Silvia Pastorekova1,2*

Institute of Virology, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava,1 Centre for Molecular Medicine, Vlarska 3-7, 831 01 Bratislava, Slovak Republic2

Received 12 February 2009/ Accepted 22 May 2009

Lymphocytic choriomeningitis virus (LCMV) is a prototypic arenavirus containing a bisegmented single-stranded RNA genome with an ambisense coding strategy. MX is a noncytolytic LCMV strain with an in vitro host range restricted to only few cell lines. MX LCMV spreads via cell-cell contacts and causes persistent infection with high production of viral nucleoprotein (NP). Using a proteomic approach, we identified keratin 1 (K1), an intermediate filament network component, as a binding partner of the viral NP. The functional significance of this interaction has been examined by chemical disruption of the keratin network, resulting in a reduced spread of MX LCMV in HeLa cells. However, K1 disassembly was considerably lower in MX LCMV-infected cells than in noninfected counterparts, indicating that NP can stabilize the keratin network and thereby support the integrity of cytoskeleton. The presence of NP also resulted in increased formation of desmosomes and stronger cell-cell adhesion. Similar effects were observed in HeLa cells persistently infected with LCMV strain Armstrong. Our findings suggest that the keratin network is important for the intercellular transmission of persistent LCMV infection in epithelial cells and show that the virus can actively facilitate its own intercellular spread through the interaction between the viral NP and K1 and stimulation of cell-cell contacts.


* Corresponding author. Mailing address: Institute of Virology, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic. Phone: 421-2-59302404. Fax: 421-2-54774284. E-mail: virusipa{at}savba.sk

{triangledown} Published ahead of print on 3 June 2009.


Journal of Virology, August 2009, p. 7842-7849, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00309-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.