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Genetic determinants of virulence in pathogenic lineage 2 West Nile virus strains.

Botha EM, Markotter W, Wolfaardt M, Paweska JT, Swanepoel R, Palacios G, Nel LH, Venter M - Emerging Infect. Dis. (2008)

Bottom Line: Phylogenetic and amino acid comparison of highly and less neuroinvasive lineage 2 strains demonstrated that the nonstructural genes, especially the nonstructural protein 5 gene, were most variable.All South African lineage 2 strains possessed the envelope-protein glycosylation site previously postulated to be associated with virulence.Major deletions existed in the 3 noncoding region of 2 lineage 2 strains previously shown to be either less or not neuroinvasive relative to the highly neuroinvasive strains sequenced in this study.

View Article: PubMed Central - PubMed

Affiliation: University of Pretoria, Pretoria, South Africa.

ABSTRACT
We determined complete genome sequences of lineage 2 West Nile virus (WNV) strains isolated from patients in South Africa who had mild or severe WNV infections. These strains had previously been shown to produce either highly or less neuroinvasive infection and induced genes similar to corresponding highly or less neuroinvasive lineage 1 strains in mice. Phylogenetic and amino acid comparison of highly and less neuroinvasive lineage 2 strains demonstrated that the nonstructural genes, especially the nonstructural protein 5 gene, were most variable. All South African lineage 2 strains possessed the envelope-protein glycosylation site previously postulated to be associated with virulence. Major deletions existed in the 3 noncoding region of 2 lineage 2 strains previously shown to be either less or not neuroinvasive relative to the highly neuroinvasive strains sequenced in this study.

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A) Amino acid differences between South African lineage 2 strains of West Nile virus (WNV) strains sequenced in the present study and previously published lineage 2 strains. Strain SA381/00 is less neuroinvasive than the highly neuroinvasive strains SA93/01, H442, and SPU116/89. Light gray, hydrophobic amino acids; dark gray, hydrophilic amino acids; black, structural-determining amino acids; white blocks, deletion of the glycosylation site in the envelope protein of the B956D117B3 strain. Numbering is according to the SA381/00 genome position for specific genes. Cap, capsid; prM, premembrane; NS, nonstructural. B) Nucleotide differences in the noncoding 5′ and 3′ regions of lineage 2 strains. Numbering is according to WNV strain SA381/00. Black, deletions; gray, nucleotide differences. The length of each genome is given in the last column. (Strain AnMg798 is incomplete in the GenBank database and may thus be longer than indicated.)
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Figure 2: A) Amino acid differences between South African lineage 2 strains of West Nile virus (WNV) strains sequenced in the present study and previously published lineage 2 strains. Strain SA381/00 is less neuroinvasive than the highly neuroinvasive strains SA93/01, H442, and SPU116/89. Light gray, hydrophobic amino acids; dark gray, hydrophilic amino acids; black, structural-determining amino acids; white blocks, deletion of the glycosylation site in the envelope protein of the B956D117B3 strain. Numbering is according to the SA381/00 genome position for specific genes. Cap, capsid; prM, premembrane; NS, nonstructural. B) Nucleotide differences in the noncoding 5′ and 3′ regions of lineage 2 strains. Numbering is according to WNV strain SA381/00. Black, deletions; gray, nucleotide differences. The length of each genome is given in the last column. (Strain AnMg798 is incomplete in the GenBank database and may thus be longer than indicated.)

Mentions: Few amino acid differences were observed between the structural proteins of the South African strains (Figure 2). SA381/00 had only 1 difference in the premembrane (prM) protein at position 105 relative to the highly neuroinvasive strains (Ala105Val) (Figure 2). Two differences, (Ala54Gly and Thr70Pro) could result in structural changes in the E protein of H442, which was isolated 50 years earlier than strains SPU116/89, SA93/01, and SA381/00. The attenuated lineage 2 strain B956D117B3 and the non-neuroinvasive Madagascar strain AnMg798 contained differences in the glycosylation site of the E protein relative to the South African strains (residues 154–157 deleted in B956D117B3, and Ser156Pro in AnMg798). Either of these changes would prevent glycosylation. Further substitutions of hydrophilic amino acids for proline and glycine residues with potentially structural implications were found in AnMg798 at positions 156, 199, and 230.


Genetic determinants of virulence in pathogenic lineage 2 West Nile virus strains.

Botha EM, Markotter W, Wolfaardt M, Paweska JT, Swanepoel R, Palacios G, Nel LH, Venter M - Emerging Infect. Dis. (2008)

A) Amino acid differences between South African lineage 2 strains of West Nile virus (WNV) strains sequenced in the present study and previously published lineage 2 strains. Strain SA381/00 is less neuroinvasive than the highly neuroinvasive strains SA93/01, H442, and SPU116/89. Light gray, hydrophobic amino acids; dark gray, hydrophilic amino acids; black, structural-determining amino acids; white blocks, deletion of the glycosylation site in the envelope protein of the B956D117B3 strain. Numbering is according to the SA381/00 genome position for specific genes. Cap, capsid; prM, premembrane; NS, nonstructural. B) Nucleotide differences in the noncoding 5′ and 3′ regions of lineage 2 strains. Numbering is according to WNV strain SA381/00. Black, deletions; gray, nucleotide differences. The length of each genome is given in the last column. (Strain AnMg798 is incomplete in the GenBank database and may thus be longer than indicated.)
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Related In: Results  -  Collection

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Figure 2: A) Amino acid differences between South African lineage 2 strains of West Nile virus (WNV) strains sequenced in the present study and previously published lineage 2 strains. Strain SA381/00 is less neuroinvasive than the highly neuroinvasive strains SA93/01, H442, and SPU116/89. Light gray, hydrophobic amino acids; dark gray, hydrophilic amino acids; black, structural-determining amino acids; white blocks, deletion of the glycosylation site in the envelope protein of the B956D117B3 strain. Numbering is according to the SA381/00 genome position for specific genes. Cap, capsid; prM, premembrane; NS, nonstructural. B) Nucleotide differences in the noncoding 5′ and 3′ regions of lineage 2 strains. Numbering is according to WNV strain SA381/00. Black, deletions; gray, nucleotide differences. The length of each genome is given in the last column. (Strain AnMg798 is incomplete in the GenBank database and may thus be longer than indicated.)
Mentions: Few amino acid differences were observed between the structural proteins of the South African strains (Figure 2). SA381/00 had only 1 difference in the premembrane (prM) protein at position 105 relative to the highly neuroinvasive strains (Ala105Val) (Figure 2). Two differences, (Ala54Gly and Thr70Pro) could result in structural changes in the E protein of H442, which was isolated 50 years earlier than strains SPU116/89, SA93/01, and SA381/00. The attenuated lineage 2 strain B956D117B3 and the non-neuroinvasive Madagascar strain AnMg798 contained differences in the glycosylation site of the E protein relative to the South African strains (residues 154–157 deleted in B956D117B3, and Ser156Pro in AnMg798). Either of these changes would prevent glycosylation. Further substitutions of hydrophilic amino acids for proline and glycine residues with potentially structural implications were found in AnMg798 at positions 156, 199, and 230.

Bottom Line: Phylogenetic and amino acid comparison of highly and less neuroinvasive lineage 2 strains demonstrated that the nonstructural genes, especially the nonstructural protein 5 gene, were most variable.All South African lineage 2 strains possessed the envelope-protein glycosylation site previously postulated to be associated with virulence.Major deletions existed in the 3 noncoding region of 2 lineage 2 strains previously shown to be either less or not neuroinvasive relative to the highly neuroinvasive strains sequenced in this study.

View Article: PubMed Central - PubMed

Affiliation: University of Pretoria, Pretoria, South Africa.

ABSTRACT
We determined complete genome sequences of lineage 2 West Nile virus (WNV) strains isolated from patients in South Africa who had mild or severe WNV infections. These strains had previously been shown to produce either highly or less neuroinvasive infection and induced genes similar to corresponding highly or less neuroinvasive lineage 1 strains in mice. Phylogenetic and amino acid comparison of highly and less neuroinvasive lineage 2 strains demonstrated that the nonstructural genes, especially the nonstructural protein 5 gene, were most variable. All South African lineage 2 strains possessed the envelope-protein glycosylation site previously postulated to be associated with virulence. Major deletions existed in the 3 noncoding region of 2 lineage 2 strains previously shown to be either less or not neuroinvasive relative to the highly neuroinvasive strains sequenced in this study.

Show MeSH
Related in: MedlinePlus