Molecular determinants of virulence of West Nile virus in North America.

David Beasley, C. T. Davis, M. Whiteman, B. Granwehr, R. M. Kinney, Alan Barrett

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

West Nile virus (WNV) is a mosquito-borne flavivirus that until very recently had not been found in the Americas. In 1999, there was an outbreak of West Nile encephalitis in New York and surrounding areas, involving 62 human cases, including 7 fatalities. The virus has subsequently become established in the United States of America (U.S.) with 4156 human cases, including 284 deaths, in 2002. The WNV strains found in the U.S. are members of "lineage I", a genetic grouping that includes viruses from Europe, Asia and Africa. Molecular epidemiologic studies indicate that two genetic variants of WNV emerged in 2002. The major genetic variant is found in most parts of the U.S., while the minor genetic variant has been identified only on the southeast coast of Texas. Investigation of WNV in mouse and hamster models demonstrated that strains from the U.S. are highly neurovirulent and neuroinvasive in these laboratory rodents. Other strains, such as Ethiopia 76a from lineage I, are not neuroinvasive and represent important viruses which can be used to elucidate the molecular basis of virulence and attenuation of WNV. To identify putative molecular determinants of virulence and attenuation, we have undertaken comparative nucleotide sequencing of Ethiopia 76a and strains from the U.S. The results show that the two viruses differ by 5 amino acids in the envelope (E) protein, including loss of the glycosylation site. Comparison of our panel of 27 WNV strains suggests that E protein glycosylation is a major determinant of the mouse neuroinvasive phenotype.

Original languageEnglish (US)
Pages (from-to)35-41
Number of pages7
JournalArchives of virology. Supplementum
Issue number18
StatePublished - 2004

Fingerprint

West Nile virus
North America
Virulence
Viruses
Ethiopia
Glycosylation
Flavivirus
Encephalitis
Culicidae
Cricetinae
Disease Outbreaks
Epidemiologic Studies
Rodentia
Nucleotides
Phenotype
Amino Acids
Proteins

ASJC Scopus subject areas

  • Immunology and Microbiology(all)

Cite this

Molecular determinants of virulence of West Nile virus in North America. / Beasley, David; Davis, C. T.; Whiteman, M.; Granwehr, B.; Kinney, R. M.; Barrett, Alan.

In: Archives of virology. Supplementum, No. 18, 2004, p. 35-41.

Research output: Contribution to journalArticle

Beasley, David ; Davis, C. T. ; Whiteman, M. ; Granwehr, B. ; Kinney, R. M. ; Barrett, Alan. / Molecular determinants of virulence of West Nile virus in North America. In: Archives of virology. Supplementum. 2004 ; No. 18. pp. 35-41.
@article{64f906113da24db0a63ca5da74429f72,
title = "Molecular determinants of virulence of West Nile virus in North America.",
abstract = "West Nile virus (WNV) is a mosquito-borne flavivirus that until very recently had not been found in the Americas. In 1999, there was an outbreak of West Nile encephalitis in New York and surrounding areas, involving 62 human cases, including 7 fatalities. The virus has subsequently become established in the United States of America (U.S.) with 4156 human cases, including 284 deaths, in 2002. The WNV strains found in the U.S. are members of {"}lineage I{"}, a genetic grouping that includes viruses from Europe, Asia and Africa. Molecular epidemiologic studies indicate that two genetic variants of WNV emerged in 2002. The major genetic variant is found in most parts of the U.S., while the minor genetic variant has been identified only on the southeast coast of Texas. Investigation of WNV in mouse and hamster models demonstrated that strains from the U.S. are highly neurovirulent and neuroinvasive in these laboratory rodents. Other strains, such as Ethiopia 76a from lineage I, are not neuroinvasive and represent important viruses which can be used to elucidate the molecular basis of virulence and attenuation of WNV. To identify putative molecular determinants of virulence and attenuation, we have undertaken comparative nucleotide sequencing of Ethiopia 76a and strains from the U.S. The results show that the two viruses differ by 5 amino acids in the envelope (E) protein, including loss of the glycosylation site. Comparison of our panel of 27 WNV strains suggests that E protein glycosylation is a major determinant of the mouse neuroinvasive phenotype.",
author = "David Beasley and Davis, {C. T.} and M. Whiteman and B. Granwehr and Kinney, {R. M.} and Alan Barrett",
year = "2004",
language = "English (US)",
pages = "35--41",
journal = "Archives of virology. Supplementum.",
issn = "0939-1983",
publisher = "Springer Verlag",
number = "18",

}

TY - JOUR

T1 - Molecular determinants of virulence of West Nile virus in North America.

AU - Beasley, David

AU - Davis, C. T.

AU - Whiteman, M.

AU - Granwehr, B.

AU - Kinney, R. M.

AU - Barrett, Alan

PY - 2004

Y1 - 2004

N2 - West Nile virus (WNV) is a mosquito-borne flavivirus that until very recently had not been found in the Americas. In 1999, there was an outbreak of West Nile encephalitis in New York and surrounding areas, involving 62 human cases, including 7 fatalities. The virus has subsequently become established in the United States of America (U.S.) with 4156 human cases, including 284 deaths, in 2002. The WNV strains found in the U.S. are members of "lineage I", a genetic grouping that includes viruses from Europe, Asia and Africa. Molecular epidemiologic studies indicate that two genetic variants of WNV emerged in 2002. The major genetic variant is found in most parts of the U.S., while the minor genetic variant has been identified only on the southeast coast of Texas. Investigation of WNV in mouse and hamster models demonstrated that strains from the U.S. are highly neurovirulent and neuroinvasive in these laboratory rodents. Other strains, such as Ethiopia 76a from lineage I, are not neuroinvasive and represent important viruses which can be used to elucidate the molecular basis of virulence and attenuation of WNV. To identify putative molecular determinants of virulence and attenuation, we have undertaken comparative nucleotide sequencing of Ethiopia 76a and strains from the U.S. The results show that the two viruses differ by 5 amino acids in the envelope (E) protein, including loss of the glycosylation site. Comparison of our panel of 27 WNV strains suggests that E protein glycosylation is a major determinant of the mouse neuroinvasive phenotype.

AB - West Nile virus (WNV) is a mosquito-borne flavivirus that until very recently had not been found in the Americas. In 1999, there was an outbreak of West Nile encephalitis in New York and surrounding areas, involving 62 human cases, including 7 fatalities. The virus has subsequently become established in the United States of America (U.S.) with 4156 human cases, including 284 deaths, in 2002. The WNV strains found in the U.S. are members of "lineage I", a genetic grouping that includes viruses from Europe, Asia and Africa. Molecular epidemiologic studies indicate that two genetic variants of WNV emerged in 2002. The major genetic variant is found in most parts of the U.S., while the minor genetic variant has been identified only on the southeast coast of Texas. Investigation of WNV in mouse and hamster models demonstrated that strains from the U.S. are highly neurovirulent and neuroinvasive in these laboratory rodents. Other strains, such as Ethiopia 76a from lineage I, are not neuroinvasive and represent important viruses which can be used to elucidate the molecular basis of virulence and attenuation of WNV. To identify putative molecular determinants of virulence and attenuation, we have undertaken comparative nucleotide sequencing of Ethiopia 76a and strains from the U.S. The results show that the two viruses differ by 5 amino acids in the envelope (E) protein, including loss of the glycosylation site. Comparison of our panel of 27 WNV strains suggests that E protein glycosylation is a major determinant of the mouse neuroinvasive phenotype.

UR - http://www.scopus.com/inward/record.url?scp=3042525251&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042525251&partnerID=8YFLogxK

M3 - Article

C2 - 15119761

AN - SCOPUS:3042525251

SP - 35

EP - 41

JO - Archives of virology. Supplementum.

JF - Archives of virology. Supplementum.

SN - 0939-1983

IS - 18

ER -