The old world and new world alphaviruses use different virus-specific proteins for induction of transcriptional shutoff

Natalia Garmashova, Rodion Gorchakov, Eugenia Volkova, Slobodan Paessler, Elena Frolova, Ilya Frolov

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Alphaviruses are widely distributed throughout the world. During the last few thousand years, the New World viruses, including Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), evolved separately from those of the Old World, i.e., Sindbis virus (SINV) and Semliki Forest virus (SFV). Nevertheless, the results of our study indicate that both groups have developed the same characteristic: their replication efficiently interferes with cellular transcription and the cell response to virus replication. Transcriptional shutoff caused by at least two of the Old World alphaviruses, SINV and SFV, which belong to different serological complexes, depends on nsP2, but not on the capsid protein, functioning. Our data suggest that the New World alphaviruses VEEV and EEEV developed an alternative mechanism of transcription inhibition that is mainly determined by their capsid protein, but not by the nsP2. The ability of the VEEV capsid to inhibit cellular transcription appears to be controlled by the amino-terminal fragment of the protein, but not by its protease activity or by the positively charged RNA-binding domain. These data provide new insights into alphavirus evolution and present a plausible explanation for the particular recombination events that led to the formation of western equine encephalitis virus (WEEV) from SINV- and EEEV-like ancestors. The recombination allowed WEEV to acquire capsid protein functioning in transcription inhibition from EEEV-like vims. Identification of the new functions in the New World alphavirus-derived capsids opens an opportunity for developing new, safer alphavirus-based gene expression systems and designing new types of attenuated vaccine strains of VEEV and EEEV.

Original languageEnglish (US)
Pages (from-to)2472-2484
Number of pages13
JournalJournal of Virology
Volume81
Issue number5
DOIs
StatePublished - Mar 2007

Fingerprint

Alphavirus
Eastern equine encephalitis virus
Venezuelan Equine Encephalitis Viruses
Venezuelan equine encephalitis virus
Sindbis virus
Sindbis Virus
Viruses
viruses
Capsid Proteins
Western Equine Encephalitis Viruses
transcription (genetics)
Semliki Forest virus
coat proteins
Western equine encephalitis virus
Semliki forest virus
Proteins
capsid
proteins
Capsid
Genetic Recombination

ASJC Scopus subject areas

  • Immunology

Cite this

The old world and new world alphaviruses use different virus-specific proteins for induction of transcriptional shutoff. / Garmashova, Natalia; Gorchakov, Rodion; Volkova, Eugenia; Paessler, Slobodan; Frolova, Elena; Frolov, Ilya.

In: Journal of Virology, Vol. 81, No. 5, 03.2007, p. 2472-2484.

Research output: Contribution to journalArticle

Garmashova, Natalia ; Gorchakov, Rodion ; Volkova, Eugenia ; Paessler, Slobodan ; Frolova, Elena ; Frolov, Ilya. / The old world and new world alphaviruses use different virus-specific proteins for induction of transcriptional shutoff. In: Journal of Virology. 2007 ; Vol. 81, No. 5. pp. 2472-2484.
@article{7d42d1a2ca2748da8581a96a77ed3d7d,
title = "The old world and new world alphaviruses use different virus-specific proteins for induction of transcriptional shutoff",
abstract = "Alphaviruses are widely distributed throughout the world. During the last few thousand years, the New World viruses, including Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), evolved separately from those of the Old World, i.e., Sindbis virus (SINV) and Semliki Forest virus (SFV). Nevertheless, the results of our study indicate that both groups have developed the same characteristic: their replication efficiently interferes with cellular transcription and the cell response to virus replication. Transcriptional shutoff caused by at least two of the Old World alphaviruses, SINV and SFV, which belong to different serological complexes, depends on nsP2, but not on the capsid protein, functioning. Our data suggest that the New World alphaviruses VEEV and EEEV developed an alternative mechanism of transcription inhibition that is mainly determined by their capsid protein, but not by the nsP2. The ability of the VEEV capsid to inhibit cellular transcription appears to be controlled by the amino-terminal fragment of the protein, but not by its protease activity or by the positively charged RNA-binding domain. These data provide new insights into alphavirus evolution and present a plausible explanation for the particular recombination events that led to the formation of western equine encephalitis virus (WEEV) from SINV- and EEEV-like ancestors. The recombination allowed WEEV to acquire capsid protein functioning in transcription inhibition from EEEV-like vims. Identification of the new functions in the New World alphavirus-derived capsids opens an opportunity for developing new, safer alphavirus-based gene expression systems and designing new types of attenuated vaccine strains of VEEV and EEEV.",
author = "Natalia Garmashova and Rodion Gorchakov and Eugenia Volkova and Slobodan Paessler and Elena Frolova and Ilya Frolov",
year = "2007",
month = "3",
doi = "10.1128/JVI.02073-06",
language = "English (US)",
volume = "81",
pages = "2472--2484",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - The old world and new world alphaviruses use different virus-specific proteins for induction of transcriptional shutoff

AU - Garmashova, Natalia

AU - Gorchakov, Rodion

AU - Volkova, Eugenia

AU - Paessler, Slobodan

AU - Frolova, Elena

AU - Frolov, Ilya

PY - 2007/3

Y1 - 2007/3

N2 - Alphaviruses are widely distributed throughout the world. During the last few thousand years, the New World viruses, including Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), evolved separately from those of the Old World, i.e., Sindbis virus (SINV) and Semliki Forest virus (SFV). Nevertheless, the results of our study indicate that both groups have developed the same characteristic: their replication efficiently interferes with cellular transcription and the cell response to virus replication. Transcriptional shutoff caused by at least two of the Old World alphaviruses, SINV and SFV, which belong to different serological complexes, depends on nsP2, but not on the capsid protein, functioning. Our data suggest that the New World alphaviruses VEEV and EEEV developed an alternative mechanism of transcription inhibition that is mainly determined by their capsid protein, but not by the nsP2. The ability of the VEEV capsid to inhibit cellular transcription appears to be controlled by the amino-terminal fragment of the protein, but not by its protease activity or by the positively charged RNA-binding domain. These data provide new insights into alphavirus evolution and present a plausible explanation for the particular recombination events that led to the formation of western equine encephalitis virus (WEEV) from SINV- and EEEV-like ancestors. The recombination allowed WEEV to acquire capsid protein functioning in transcription inhibition from EEEV-like vims. Identification of the new functions in the New World alphavirus-derived capsids opens an opportunity for developing new, safer alphavirus-based gene expression systems and designing new types of attenuated vaccine strains of VEEV and EEEV.

AB - Alphaviruses are widely distributed throughout the world. During the last few thousand years, the New World viruses, including Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), evolved separately from those of the Old World, i.e., Sindbis virus (SINV) and Semliki Forest virus (SFV). Nevertheless, the results of our study indicate that both groups have developed the same characteristic: their replication efficiently interferes with cellular transcription and the cell response to virus replication. Transcriptional shutoff caused by at least two of the Old World alphaviruses, SINV and SFV, which belong to different serological complexes, depends on nsP2, but not on the capsid protein, functioning. Our data suggest that the New World alphaviruses VEEV and EEEV developed an alternative mechanism of transcription inhibition that is mainly determined by their capsid protein, but not by the nsP2. The ability of the VEEV capsid to inhibit cellular transcription appears to be controlled by the amino-terminal fragment of the protein, but not by its protease activity or by the positively charged RNA-binding domain. These data provide new insights into alphavirus evolution and present a plausible explanation for the particular recombination events that led to the formation of western equine encephalitis virus (WEEV) from SINV- and EEEV-like ancestors. The recombination allowed WEEV to acquire capsid protein functioning in transcription inhibition from EEEV-like vims. Identification of the new functions in the New World alphavirus-derived capsids opens an opportunity for developing new, safer alphavirus-based gene expression systems and designing new types of attenuated vaccine strains of VEEV and EEEV.

UR - http://www.scopus.com/inward/record.url?scp=33847199327&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847199327&partnerID=8YFLogxK

U2 - 10.1128/JVI.02073-06

DO - 10.1128/JVI.02073-06

M3 - Article

C2 - 17108023

AN - SCOPUS:33847199327

VL - 81

SP - 2472

EP - 2484

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 5

ER -