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Viruses 2012, 4(10), 2137-2161; doi:10.3390/v4102137

D471G Mutation in LCMV-NP Affects Its Ability to Self-associate and Results in a Dominant Negative Effect in Viral RNA Synthesis

1
Department of Microbiology and Immunology, University of Rochester, 601 Elmwood Avenue, Rochester, New York 14642, USA
2
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA
*
Author to whom correspondence should be addressed.
Received: 9 August 2012 / Revised: 21 September 2012 / Accepted: 26 September 2012 / Published: 16 October 2012
(This article belongs to the Special Issue Arenaviruses)
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Abstract

Arenaviruses merit significant interest because several family members are etiological agents of severe hemorrhagic fevers, representing a major burden to public health. Currently, there are no FDA-licensed vaccines against arenaviruses and the only available antiviral therapy is limited to the use of ribavirin that is partially effective. Arenavirus nucleoprotein (NP) is found associated with the genomic RNA forming the viral ribonucleoproteins (vRNPs) that together with the polymerase (L) direct viral replication and transcription. Virion formation requires the recruitment of vRNPs into budding sites, a process in which the arenavirus matrix-like protein (Z) plays a major role. Therefore, proper NP-NP and NP-Z interactions are required for the generation of infectious progeny. In this work we demonstrate the role of the amino acid residue D471 in the self-association of lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP). Amino acid substitutions at this position abrogate NP oligomerization, affecting its ability to mediate replication and transcription of a minigenome reporter plasmid. However, its ability to interact with the Z protein, counteract the cellular interferon response and bind to dsRNA analogs was retained. Additionally, we also document the dominant negative effect of D471G mutation on viral infection, suggesting that NP self-association is an excellent target for the development of new antivirals against arenaviruses. View Full-Text
Keywords: lymphocytic choriomeningitis virus; nucleoprotein; Z matrix protein; self-association; viral-like particles; minigenome; type I Interferon; double-stranded RNA; dominant negative lymphocytic choriomeningitis virus; nucleoprotein; Z matrix protein; self-association; viral-like particles; minigenome; type I Interferon; double-stranded RNA; dominant negative
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Ortiz-Riaño, E.; Cheng, B.Y.; Torre, J.C.; Martínez-Sobrido, L. D471G Mutation in LCMV-NP Affects Its Ability to Self-associate and Results in a Dominant Negative Effect in Viral RNA Synthesis. Viruses 2012, 4, 2137-2161.

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