Noncytopathic replication of Venezuelan equine encephalitis virus and eastern equine encephalitis virus replicons in mammalian cells

Olga Petrakova, Eugenia Volkova, Rodion Gorchakov, Slobodan Paessler, Richard M. Kinney, Ilya Frolov

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Venezuelan equine encephalitis (VEE) and eastern equine encephalitis (EEE) viruses are important, naturally emerging zoonotic viruses. They are significant human and equine pathogens which still pose a serious public health threat. Both VEE and EEE cause chronic infection in mosquitoes and persistent or chronic infection in mosquito-derived cell lines. In contrast, vertebrate hosts infected with either virus develop an acute infection with high-titer viremia and encephalitis, followed by host death or virus clearance by the immune system. Accordingly, EEE and VEE infection in vertebrate cell lines is highly cytopathic. To further understand the pathogenesis of alphaviruses on molecular and cellular levels, we designed EEE- and VEE-based replicons and investigated their replication and their ability to generate cytopathic effect (CPE) and to interfere with other viral infections. VEE and EEE replicons appeared to be less cytopathic than Sindbis virus-based constructs that we designed in our previous research and readily established persistent replication in BHK-21 cells. VEE replicons required additional mutations in the 5′ untranslated region and nsP2 or nsP3 genes to further reduce cytopathicity and to become capable of persisting in cells with no defects in alpha/beta interferon production or signaling. The results indicated that alphaviruses strongly differ in virus-host cell interactions, and the ability to cause CPE in tissue culture does not necessarily correlate with pathogenesis and strongly depends on the sequence of viral nonstructural proteins.

Original languageEnglish (US)
Pages (from-to)7597-7608
Number of pages12
JournalJournal of Virology
Volume79
Issue number12
DOIs
StatePublished - Jun 2005

Fingerprint

Venezuelan Equine Encephalomyelitides
Eastern equine encephalitis virus
Venezuelan Equine Encephalitis Viruses
Venezuelan equine encephalitis virus
replicon
Replicon
Eastern Equine Encephalomyelitis
encephalitis
horses
Alphavirus
Viruses
cells
Culicidae
Vertebrates
Viral Nonstructural Proteins
Infection
Sindbis Virus
viruses
infection
cytopathogenicity

ASJC Scopus subject areas

  • Immunology

Cite this

Noncytopathic replication of Venezuelan equine encephalitis virus and eastern equine encephalitis virus replicons in mammalian cells. / Petrakova, Olga; Volkova, Eugenia; Gorchakov, Rodion; Paessler, Slobodan; Kinney, Richard M.; Frolov, Ilya.

In: Journal of Virology, Vol. 79, No. 12, 06.2005, p. 7597-7608.

Research output: Contribution to journalArticle

Petrakova, Olga ; Volkova, Eugenia ; Gorchakov, Rodion ; Paessler, Slobodan ; Kinney, Richard M. ; Frolov, Ilya. / Noncytopathic replication of Venezuelan equine encephalitis virus and eastern equine encephalitis virus replicons in mammalian cells. In: Journal of Virology. 2005 ; Vol. 79, No. 12. pp. 7597-7608.
@article{1ab1fed4997b4fafbeb86c6a0d0ddb9c,
title = "Noncytopathic replication of Venezuelan equine encephalitis virus and eastern equine encephalitis virus replicons in mammalian cells",
abstract = "Venezuelan equine encephalitis (VEE) and eastern equine encephalitis (EEE) viruses are important, naturally emerging zoonotic viruses. They are significant human and equine pathogens which still pose a serious public health threat. Both VEE and EEE cause chronic infection in mosquitoes and persistent or chronic infection in mosquito-derived cell lines. In contrast, vertebrate hosts infected with either virus develop an acute infection with high-titer viremia and encephalitis, followed by host death or virus clearance by the immune system. Accordingly, EEE and VEE infection in vertebrate cell lines is highly cytopathic. To further understand the pathogenesis of alphaviruses on molecular and cellular levels, we designed EEE- and VEE-based replicons and investigated their replication and their ability to generate cytopathic effect (CPE) and to interfere with other viral infections. VEE and EEE replicons appeared to be less cytopathic than Sindbis virus-based constructs that we designed in our previous research and readily established persistent replication in BHK-21 cells. VEE replicons required additional mutations in the 5′ untranslated region and nsP2 or nsP3 genes to further reduce cytopathicity and to become capable of persisting in cells with no defects in alpha/beta interferon production or signaling. The results indicated that alphaviruses strongly differ in virus-host cell interactions, and the ability to cause CPE in tissue culture does not necessarily correlate with pathogenesis and strongly depends on the sequence of viral nonstructural proteins.",
author = "Olga Petrakova and Eugenia Volkova and Rodion Gorchakov and Slobodan Paessler and Kinney, {Richard M.} and Ilya Frolov",
year = "2005",
month = "6",
doi = "10.1128/JVI.79.12.7597-7608.2005",
language = "English (US)",
volume = "79",
pages = "7597--7608",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Noncytopathic replication of Venezuelan equine encephalitis virus and eastern equine encephalitis virus replicons in mammalian cells

AU - Petrakova, Olga

AU - Volkova, Eugenia

AU - Gorchakov, Rodion

AU - Paessler, Slobodan

AU - Kinney, Richard M.

AU - Frolov, Ilya

PY - 2005/6

Y1 - 2005/6

N2 - Venezuelan equine encephalitis (VEE) and eastern equine encephalitis (EEE) viruses are important, naturally emerging zoonotic viruses. They are significant human and equine pathogens which still pose a serious public health threat. Both VEE and EEE cause chronic infection in mosquitoes and persistent or chronic infection in mosquito-derived cell lines. In contrast, vertebrate hosts infected with either virus develop an acute infection with high-titer viremia and encephalitis, followed by host death or virus clearance by the immune system. Accordingly, EEE and VEE infection in vertebrate cell lines is highly cytopathic. To further understand the pathogenesis of alphaviruses on molecular and cellular levels, we designed EEE- and VEE-based replicons and investigated their replication and their ability to generate cytopathic effect (CPE) and to interfere with other viral infections. VEE and EEE replicons appeared to be less cytopathic than Sindbis virus-based constructs that we designed in our previous research and readily established persistent replication in BHK-21 cells. VEE replicons required additional mutations in the 5′ untranslated region and nsP2 or nsP3 genes to further reduce cytopathicity and to become capable of persisting in cells with no defects in alpha/beta interferon production or signaling. The results indicated that alphaviruses strongly differ in virus-host cell interactions, and the ability to cause CPE in tissue culture does not necessarily correlate with pathogenesis and strongly depends on the sequence of viral nonstructural proteins.

AB - Venezuelan equine encephalitis (VEE) and eastern equine encephalitis (EEE) viruses are important, naturally emerging zoonotic viruses. They are significant human and equine pathogens which still pose a serious public health threat. Both VEE and EEE cause chronic infection in mosquitoes and persistent or chronic infection in mosquito-derived cell lines. In contrast, vertebrate hosts infected with either virus develop an acute infection with high-titer viremia and encephalitis, followed by host death or virus clearance by the immune system. Accordingly, EEE and VEE infection in vertebrate cell lines is highly cytopathic. To further understand the pathogenesis of alphaviruses on molecular and cellular levels, we designed EEE- and VEE-based replicons and investigated their replication and their ability to generate cytopathic effect (CPE) and to interfere with other viral infections. VEE and EEE replicons appeared to be less cytopathic than Sindbis virus-based constructs that we designed in our previous research and readily established persistent replication in BHK-21 cells. VEE replicons required additional mutations in the 5′ untranslated region and nsP2 or nsP3 genes to further reduce cytopathicity and to become capable of persisting in cells with no defects in alpha/beta interferon production or signaling. The results indicated that alphaviruses strongly differ in virus-host cell interactions, and the ability to cause CPE in tissue culture does not necessarily correlate with pathogenesis and strongly depends on the sequence of viral nonstructural proteins.

UR - http://www.scopus.com/inward/record.url?scp=19944373420&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19944373420&partnerID=8YFLogxK

U2 - 10.1128/JVI.79.12.7597-7608.2005

DO - 10.1128/JVI.79.12.7597-7608.2005

M3 - Article

C2 - 15919912

AN - SCOPUS:19944373420

VL - 79

SP - 7597

EP - 7608

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 12

ER -