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PMID: 15596819 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

La Crosse virus nonstructural protein NSs counteracts the effects of short interfering RNA.

Journal of virology ·Vol. 79 ·No. 1 ·2005-01-00 ·Pages 234-44

Soldan SS, Plassmeyer ML, Matukonis MK, González-Scarano F

Abstract

Through a process known as RNA interference (RNAi), double-stranded short interfering RNAs (siRNAs) silence gene expression in a sequence-specific manner. Recently, several viral proteins, including the nonstructural protein NSs of tomato spotted wilt virus (a plant-infecting bunyavirus), the interferon antagonist protein NS1 of influenza virus, and the E3L protein of vaccinia virus, have been shown to function as suppressors of RNAi, presumably as a counterdefense against cellular mechanisms that decrease viral production. La Crosse virus (LACV), a member of the California serogroup of orthobunyaviruses, has a trisegmented negative-stranded genome comprised of large (L), medium (M), and small (S) segments. To develop a strategy for segment-specific inhibition of transcription, we designed 13 synthetic siRNAs targeting specific RNA segments of the LACV genome that decreased LACV replication and antigen expression in mammalian (293T) and insect (C6/36) cells. Furthermore, NSs, a LACV nonstructural protein, markedly inhibited RNAi directed both against an LACV M segment construct and against a host gene (glyeraldehyde-3-phosphate dehydrogenase), suggesting a possible role for this viral protein in the suppression of RNA silencing. Segment-specific siRNAs will be useful as a tool to analyze LACV transcription and replication and to obtain recombinant viruses. Additionally, NSs will help us to identify molecular pathways involved in RNAi and further define its role in the innate immune system.

MeSH Terms
Animals Base Sequence Cell Line Chlorocebus aethiops Gene Expression Regulation, Viral Glyceraldehyde-3-Phosphate Dehydrogenases/genetics,metabolism Humans La Crosse virus/genetics,metabolism,pathogenicity MicroRNAs/genetics,metabolism Molecular Sequence Data Mutation RNA Interference RNA, Messenger/genetics,metabolism RNA, Small Interfering/genetics,metabolism Transfection Vero Cells Viral Nonstructural Proteins/genetics,metabolism Viral Plaque Assay Virus Replication
Chemicals
MicroRNAs RNA, Messenger RNA, Small Interfering Viral Nonstructural Proteins Glyceraldehyde-3-Phosphate Dehydrogenases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Soldan Samantha S
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283, USA.
Plassmeyer Matthew L
Matukonis Meghan K
González-Scarano Francisco
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.79.1.234-244.2005
Published
2005-01-00
Pages
234-44
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC538693
Subset
IM
Grants
NINDS NIH HHS · P01 NS030606 · United States
NINDS NIH HHS · T32 NS007180 · United States
NIGMS NIH HHS · T32 GM-07229 · United States
NIGMS NIH HHS · T32 GM007229 · United States
NINDS NIH HHS · NS-07180 · United States
NINDS NIH HHS · NS-30606 · United States
External Links
PubMed source DOI: 10.1128/JVI.79.1.234-244.2005 PMC Full Text View journal details
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