Ebola Virus VP35 Interaction with Dynein LC8 Regulates Viral RNA Synthesis

Luthra, Priya; Jordan, David S.; Leung, Daisy W.; Amarasinghe, Gaya K.; Basler, Christopher F.

doi:10.1128/JVI.03652-14

Title: Ebola Virus VP35 Interaction with Dynein LC8 Regulates Viral RNA Synthesis

Journal Article · Fri Apr 03 00:00:00 EDT 2015 · Journal of Virology

DOI:https://doi.org/10.1128/JVI.03652-14· OSTI ID:1351394

Luthra, Priya ^[1]; Jordan, David S. ^[2]; Leung, Daisy W. ^[2]; Amarasinghe, Gaya K. ^[2]; Basler, Christopher F. ^[1]

Icahn School of Medicine at Mount Sinai, New York, NY (United States)
Washington Univ. School of Medicine, St. Louis, MO (United States)

Ebola virus VP35 inhibits alpha/beta interferon production and functions as a viral polymerase cofactor. Previously, the 8-kDa cytoplasmic dynein light chain (LC8) was demonstrated to interact with VP35, but the functional consequences were unclear. Furthermore we demonstrate that the interaction is direct and of high affinity and that binding stabilizes the VP35 N-terminal oligomerization domain and enhances viral RNA synthesis. Mutational analysis demonstrates that VP35 interaction is required for the functional effects of LC8.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH)

Grant/Contract Number:: R01AI107056; R01AI059536; U19AI109945; U19AI109664; U19 AI070489; R01AI081914; T32-CA09547-37

OSTI ID:: 1351394

Journal Information:: Journal of Virology, Vol. 89, Issue 9; ISSN 0022-538X

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 38 works

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References (28)

Structural models of DYNLL1 with interacting partners: African swine fever virus protein p54 and postsynaptic scaffolding protein gephyrin García-Mayoral, María Flor; Rodríguez-Crespo, I.; Bruix, M. FEBS Letters, Vol. 585, Issue 1 https://doi.org/10.1016/j.febslet.2010.11.027	journal	November 2010
Recognition of novel viral sequences that associate with the dynein light chain LC8 identified through a pepscan technique Martı́nez-Moreno, Mónica; Navarro-Lérida, Inmaculada; Roncal, Fernando FEBS Letters, Vol. 544, Issue 1-3 https://doi.org/10.1016/S0014-5793(03)00516-7	journal	May 2003
Dimerization of the Highly Conserved Light Chain Shared by Dynein and Myosin V Benashski, Sharon E.; Harrison, Alistair; Patel-King, Ramila S. Journal of Biological Chemistry, Vol. 272, Issue 33 https://doi.org/10.1074/jbc.272.33.20929	journal	August 1997
Cytoplasmic Dynein Contains a Family of Differentially Expressed Light Chains ^† King, Stephen M.; Barbarese, Elisa; Dillman, James F. Biochemistry, Vol. 37, Issue 43 https://doi.org/10.1021/bi9810813	journal	October 1998
Viral immune modulators perturb the human molecular network by common and unique strategies Pichlmair, Andreas; Kandasamy, Kumaran; Alvisi, Gualtiero Nature, Vol. 487, Issue 7408 https://doi.org/10.1038/nature11289	journal	July 2012
African Swine Fever Virus Protein p54 Interacts with the Microtubular Motor Complex through Direct Binding to Light-Chain Dynein Alonso, C.; Miskin, J.; Hernaez, B. Journal of Virology, Vol. 75, Issue 20 https://doi.org/10.1128/JVI.75.20.9819-9827.2001	journal	October 2001
The dynein light chain 8 binding motif of rabies virus phosphoprotein promotes efficient viral transcription Tan, G. S.; Preuss, M. A. R.; Williams, J. C. Proceedings of the National Academy of Sciences, Vol. 104, Issue 17 https://doi.org/10.1073/pnas.0701397104	journal	April 2007
Both matrix proteins of Ebola virus contribute to the regulation of viral genome replication and transcription Hoenen, T.; Jung, S.; Herwig, A. Virology, Vol. 403, Issue 1 https://doi.org/10.1016/j.virol.2010.04.002	journal	July 2010
Structure of the Ebola VP35 interferon inhibitory domain Leung, D. W.; Ginder, N. D.; Fulton, D. B. Proceedings of the National Academy of Sciences, Vol. 106, Issue 2 https://doi.org/10.1073/pnas.0807854106	journal	January 2009
Mutual Antagonism between the Ebola Virus VP35 Protein and the RIG-I Activator PACT Determines Infection Outcome Luthra, Priya; Ramanan, Parameshwaran; Mire, Chad E. Cell Host & Microbe, Vol. 14, Issue 1 https://doi.org/10.1016/j.chom.2013.06.010	journal	July 2013
The association of viral proteins with host cell dynein components during virus infection Merino‐Gracia, Javier; García‐Mayoral, María F.; Rodríguez‐Crespo, Ignacio The FEBS Journal, Vol. 278, Issue 17 https://doi.org/10.1111/j.1742-4658.2011.08252.x	journal	August 2011
The Ebola virus ribonucleoprotein complex: A novel VP30–L interaction identified Groseth, A.; Charton, J. E.; Sauerborn, M. Virus Research, Vol. 140, Issue 1-2 https://doi.org/10.1016/j.virusres.2008.10.017	journal	March 2009
The Ebola virus VP35 protein functions as a type I IFN antagonist Basler, C. F.; Wang, X.; Muhlberger, E. Proceedings of the National Academy of Sciences, Vol. 97, Issue 22 https://doi.org/10.1073/pnas.220398297	journal	October 2000
A C-terminal basic amino acid motif of Zaire ebolavirus VP35 is essential for type I interferon antagonism and displays high identity with the RNA-binding domain of another interferon antagonist, the NS1 protein of influenza A virus Hartman, Amy L.; Towner, Jonathan S.; Nichol, Stuart T. Virology, Vol. 328, Issue 2 https://doi.org/10.1016/j.virol.2004.07.006	journal	October 2004
Nucleocapsid formation and RNA synthesis of Marburg virus is dependent on two coiled coil motifs in the nucleoprotein DiCarlo, Andrea; Möller, Peggy; Lander, Angelika Virology Journal, Vol. 4, Issue 1 https://doi.org/10.1186/1743-422X-4-105	journal	January 2007
Herpes Simplex Virus Type 1 Capsid Protein VP26 Interacts with Dynein Light Chains RP3 and Tctex1 and Plays a Role in Retrograde Cellular Transport Douglas, Mark W.; Diefenbach, Russell J.; Homa, Fred L. Journal of Biological Chemistry, Vol. 279, Issue 27 https://doi.org/10.1074/jbc.M311671200	journal	April 2004
The 8-kDa Dynein Light Chain Binds to Its Targets via a Conserved (K/R) X TQT Motif Lo, Kevin W. -H.; Naisbitt, Scott; Fan, Jing-Song Journal of Biological Chemistry, Vol. 276, Issue 17 https://doi.org/10.1074/jbc.M010320200	journal	January 2001
Interactions of Marburg Virus Nucleocapsid Proteins Becker, S.; Rinne, C.; Hofsäß, U. Virology, Vol. 249, Issue 2 https://doi.org/10.1006/viro.1998.9328	journal	September 1998
Structure of the Monomeric 8-kDa Dynein Light Chain and Mechanism of the Domain-swapped Dimer Assembly Wang, Wenning; Lo, Kevin W. -H.; Kan, Ho-Man Journal of Biological Chemistry, Vol. 278, Issue 42 https://doi.org/10.1074/jbc.M307118200	journal	August 2003
The Ebola Virus VP35 Protein Inhibits Activation of Interferon Regulatory Factor 3 Basler, C. F.; Mikulasova, A.; Martinez-Sobrido, L. Journal of Virology, Vol. 77, Issue 14 https://doi.org/10.1128/JVI.77.14.7945-7956.2003	journal	July 2003
Ebolavirus VP35 Interacts with the Cytoplasmic Dynein Light Chain 8 Kubota, T.; Matsuoka, M.; Chang, T. -H. Journal of Virology, Vol. 83, Issue 13 https://doi.org/10.1128/JVI.00480-09	journal	April 2009
Identification of novel cellular proteins that bind to the LC8 dynein light chain using a pepscan technique Rodrı́guez-Crespo, Ignacio; Yélamos, Belén; Roncal, Fernando FEBS Letters, Vol. 503, Issue 2-3 https://doi.org/10.1016/S0014-5793(01)02718-1	journal	August 2001
Identification of the dynein light chains required for human papillomavirus infection: Role of dynein light chains in HPV infection Schneider, Marc A.; Spoden, Gilles A.; Florin, Luise Cellular Microbiology, Vol. 13, Issue 1 https://doi.org/10.1111/j.1462-5822.2010.01515.x	journal	December 2010
Ebolavirus VP35 is a multifunctional virulence factor Leung, Daisy W.; Prins, Kathleen C.; Basler, Christopher F. Virulence, Vol. 1, Issue 6 https://doi.org/10.4161/viru.1.6.12984	journal	November 2010
Homo-oligomerization facilitates the interferon-antagonist activity of the ebolavirus VP35 protein Reid, St. Patrick; Cárdenas, Washington B.; Basler, Christopher F. Virology, Vol. 341, Issue 2 https://doi.org/10.1016/j.virol.2005.06.044	journal	October 2005
Interaction of the Rabies Virus P Protein with the LC8 Dynein Light Chain Raux, H.; Flamand, A.; Blondel, D. Journal of Virology, Vol. 74, Issue 21 https://doi.org/10.1128/JVI.74.21.10212-10216.2000	journal	November 2000
On the Domain Structure and the Polymerization State of the Sendai Virus P Protein Tarbouriech, Nicolas; Curran, Joseph; Ebel, Christine Virology, Vol. 266, Issue 1 https://doi.org/10.1006/viro.1999.0066	journal	January 2000
Comparison of the Transcription and Replication Strategies of Marburg Virus and Ebola Virus by Using Artificial Replication Systems Mühlberger, Elke; Weik, Michael; Volchkov, Viktor E. Journal of Virology, Vol. 73, Issue 3 https://doi.org/10.1128/JVI.73.3.2333-2342.1999	journal	March 1999

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Ebola virus VP35 has novel NTPase and helicase-like activities Shu, Ting; Gan, Tianyu; Bai, Peng Nucleic Acids Research, Vol. 47, Issue 11 https://doi.org/10.1093/nar/gkz340	journal	May 2019
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