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PMID: 7679745 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Attenuation of Venezuelan equine encephalitis virus strain TC-83 is encoded by the 5'-noncoding region and the E2 envelope glycoprotein.

Journal of virology ·Vol. 67 ·No. 3 ·1993-03-00 ·Pages 1269-77

Kinney RM, Chang GJ, Tsuchiya KR, Sneider JM, Roehrig JT, Woodward TM, Trent DW

Abstract

The virulent Trinidad donkey (TRD) strain of Venezuelan equine encephalitis (VEE) virus and its live attenuated vaccine derivative, TC-83 virus, have different neurovirulence characteristics. A full-length cDNA clone of the TC-83 virus genome was constructed behind the bacteriophage T7 promoter in the polylinker of plasmid pUC18. To identify the genomic determinants of TC-83 virus attenuation, TRD virus-specific sequences were inserted into the TC-83 virus clone by in vitro mutagenesis or recombination. Antigenic analysis of recombinant viruses with VEE E2- and E1-specific monoclonal antibodies gave predicted antigenic reactivities. Mouse challenge experiments indicated that genetic markers responsible for the attenuated phenotype of TC-83 virus are composed of genome nucleotide position 3 in the 5'-noncoding region and the E2 envelope glycoprotein. TC-83 virus amino acid position E2-120 appeared to be the major structural determinant of attenuation. Insertion of the TRD virus-specific 5'-noncoding region, by itself, into the TC-83 virus full-length clone did not alter the attenuated phenotype of the virus. However, the TRD virus-specific 5'-noncoding region enhanced the virulence potential of downstream TRD virus amino acid sequences.

MeSH Terms
Animals Antibody Formation Antigens, Viral/immunology Bacteriophage T7/genetics Base Sequence Cloning, Molecular Encephalitis Virus, Venezuelan Equine/genetics,immunology,pathogenicity Encephalomyelitis, Venezuelan Equine/immunology,prevention & control Epitopes Genome, Viral Male Mice Mice, Inbred ICR Molecular Sequence Data Point Mutation Regulatory Sequences, Nucleic Acid/genetics Survival Analysis Vaccines, Attenuated Vero Cells Viral Envelope Proteins/genetics,immunology Viral Plaque Assay Virulence
Chemicals
Antigens, Viral Epitopes Vaccines, Attenuated Viral Envelope Proteins glycoprotein E2, equine encephalitis virus
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kinney R M
Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado 80522-2087.
Chang G J
Tsuchiya K R
Sneider J M
Roehrig J T
Woodward T M
Trent D W
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.3.1269-1277.1993
Published
1993-03-00
Pages
1269-77
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC237493
Subset
IM
Databases
GENBANK
L01442, L01443
External Links
PubMed source DOI: 10.1128/JVI.67.3.1269-1277.1993 PMC Full Text View journal details
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