Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

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.

SUBMITTER: Botha EM

PROVIDER: S-EPMC2600181 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

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

Botha Elizabeth M EM Markotter Wanda W Wolfaardt Mariaan M Paweska Janusz T JT Swanepoel Robert R Palacios Gustavio G Nel Louis H LH Venter Marietjie M

Emerging infectious diseases 20080201 2

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 ...[more]

PMID: 18258114

Similar Datasets

Virulence determinants between New York 99 and Kunjin strains of West Nile virus.

Project description:An attenuated Australian strain of West Nile virus (WNV), Kunjin (KUN), shares ~98% amino acid homology with the pathogenic New York 99 NY99 strain (NY99). To investigate the viral factors involved in NY99 virulence we generated an infectious cDNA clone of the WNV NY99 4132 isolate from which virus was recovered and was shown to be indistinguishable from the parental isolate. We then introduced the regions of the NY99 non-structural (NS) proteins and/or untranslated regions (UTRs) into the KUN backbone. Chimeric KUN viruses containing NY99 5'UTR and the parts of NS coding region were more virulent in mice than parental KUN virus. Chimeric NY99 viruses, containing KUN NS2A protein with alanine 30 to proline substitution were significantly less cytopathic in cells and less virulent in mice. Our results identify the 5'UTR and NS proteins as WNV virulence determinants and confirm a role for the NS2A in WNV cytopathicity and virulence.

| S-EPMC3089702 | biostudies-literature

Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 West Nile virus strains.

Project description:The introduction of West Nile virus (WNV) into North America has been associated with relatively high rates of neurological disease and death in humans, birds, horses, and some other animals. Previous studies identified strains in both genetic lineage 1 and genetic lineage 2, including North American isolates of lineage 1, that were highly virulent in a mouse neuroinvasion model, while other strains were avirulent or significantly attenuated (D. W. C. Beasley, L. Li, M. T. Suderman, and A. D. T. Barrett, Virology 296:17-23, 2002). To begin to elucidate the basis for these differences, we compared a highly virulent New York 1999 (NY99) isolate with a related Old World lineage 1 strain, An4766 (ETH76a), which is attenuated for mouse neuroinvasion. Genomic sequencing of ETH76a revealed a relatively small number of nucleotide (5.1%) and amino acid (0.6%) differences compared with NY99. These differences were located throughout the genome and included five amino acid differences in the envelope protein gene. Substitution of premembrane and envelope genes of ETH76a into a NY99 infectious clone backbone yielded a virus with altered in vitro growth characteristics and a mouse virulence phenotype comparable to ETH76a. Further site-specific mutagenesis studies revealed that the altered phenotype was primarily mediated via loss of envelope protein glycosylation and that this was associated with altered stability of the virion at mildly acidic pH. Therefore, the enhanced virulence of North American WNV strains compared with other Old World lineage 1 strains is at least partly mediated by envelope protein glycosylation.

| S-EPMC1143769 | biostudies-literature

Genetic characterization of West Nile virus lineage 2, Greece, 2010.

Project description:We conducted a complete genome analysis of a West Nile virus detected in Culex pipiens mosquitoes during a severe outbreak of human West Nile disease in Greece 2010. The virus showed closest genetic relationship to the lineage 2 strain that emerged in Hungary in 2004; increased virulence may be associated with amino acid substitution H249P.

| S-EPMC3321789 | biostudies-literature

Lineage 1 and 2 strains of encephalitic West Nile virus, central Europe.

Project description:Two different West Nile virus (WNV) strains caused lethal encephalitis in a flock of geese and a goshawk in southeastern Hungary in 2003 and 2004, respectively. During the outbreak in geese, 14 confirmed human cases of WNV encephalitis and meningitis were reported in the same area. Sequencing of complete genomes of both WNV strains and phylogenetic analyses showed that the goose-derived strain exhibits closest genetic relationship to strains isolated in 1998 in Israel and to the strain that emerged in 1999 in the United States. WNV derived from the goshawk showed the highest identity to WNV strains of lineage 2 isolated in central Africa. The same strain reemerged in 2005 in the same location, which suggests that the virus may have overwintered in Europe. The emergence of an exotic WNV strain in Hungary emphasizes the role of migrating birds in introducing new viruses to Europe.

| S-EPMC3294705 | biostudies-literature

Partial genetic characterization of West Nile virus strains, New York State, 2000.

Project description:We analyzed nucleotide sequences from the envelope gene of 11 West Nile (WN) virus strains collected in New York State during the 2000 transmission season to determine whether they differed genetically from each other and from the initial strain isolated in 1999. The complete envelope genes of these strains were amplified by reverse transcription-polymerase chain reaction. The resulting sequences were aligned, the genetic distances were computed, and a phylogenetic tree was constructed. Ten (0.7%) of 1,503 positions in the envelope gene were polymorphic in one or more sequences. The genetic distances were 0.003 or less. WN virus strains circulating in 2000 were homogeneous with respect to one another and to a strain isolated in 1999.

| S-EPMC2631742 | biostudies-other

Molecular Determinants of West Nile Virus Virulence and Pathogenesis in Vertebrate and Invertebrate Hosts.

Project description:West Nile virus (WNV), like the dengue virus (DENV) and yellow fever virus (YFV), are major arboviruses belonging to the Flavivirus genus. WNV is emerging or endemic in many countries around the world, affecting humans and other vertebrates. Since 1999, it has been considered to be a major public and veterinary health problem, causing diverse pathologies, ranging from a mild febrile state to severe neurological damage and death. WNV is transmitted in a bird-mosquito-bird cycle, and can occasionally infect humans and horses, both highly susceptible to the virus but considered dead-end hosts. Many studies have investigated the molecular determinants of WNV virulence, mainly with the ultimate objective of guiding vaccine development. Several vaccines are used in horses in different parts of the world, but there are no licensed WNV vaccines for humans, suggesting the need for greater understanding of the molecular determinants of virulence and antigenicity in different hosts. Owing to technical and economic considerations, WNV virulence factors have essentially been studied in rodent models, and the results cannot always be transported to mosquito vectors or to avian hosts. In this review, the known molecular determinants of WNV virulence, according to invertebrate (mosquitoes) or vertebrate hosts (mammalian and avian), are presented and discussed. This overview will highlight the differences and similarities found between WNV hosts and models, to provide a foundation for the prediction and anticipation of WNV re-emergence and its risk of global spread.

| S-EPMC7731113 | biostudies-literature

Molecular evolution of lineage 2 West Nile virus.

Project description:Since the 1990s West Nile virus (WNV) has become an increasingly important public health problem and the cause of outbreaks of neurological disease. Genetic analyses have identified multiple lineages with many studies focusing on lineage 1 due to its emergence in New York in 1999 and its neuroinvasive phenotype. Until recently, viruses in lineage 2 were not thought to be of public health importance due to few outbreaks of disease being associated with viruses in this lineage. However, recent epidemics of lineage 2 in Europe (Greece and Italy) and Russia have shown the increasing importance of this lineage. There are very few genetic studies examining isolates belonging to lineage 2. We have sequenced the full-length genomes of four older lineage 2 WNV isolates, compared them to 12 previously published genomic sequences and examined the evolution of this lineage. Our studies show that this lineage has evolved over the past 300-400 years and appears to correlate with a change from mouse attenuated to virulent phenotype based on previous studies by our group. This evolution mirrors that which is seen in lineage 1 isolates, which have also evolved to a virulent phenotype over the same period of time.

| S-EPMC3709619 | biostudies-literature

West Nile Virus Lineage 2 Overwintering in Italy.

Project description:In January 2022, West Nile virus (WNV) lineage 2 (L2) was detected in an adult female goshawk rescued near Perugia in the region of Umbria (Italy). The animal showed neurological symptoms and died 15 days after its recovery in a wildlife rescue center. This was the second case of WNV infection recorded in birds in the Umbria region during the cold season, when mosquitoes, the main WNV vectors, are usually not active. According to the National Surveillance Plan, the Umbria region is included amongst the WNV low-risk areas. The necropsy evidenced generalized pallor of the mucous membranes, mild splenomegaly, and cerebral edema. WNV L2 was detected in the brain, heart, kidney, and spleen homogenate using specific RT-PCR. Subsequently, the extracted viral RNA was sequenced. A Bayesian phylogenetic analysis performed through a maximum-likelihood tree showed that the genome sequence clustered with the Italian strains within the European WNV strains among the central-southern European WNV L2 clade. These results, on the one hand, confirmed that the WNV L2 strains circulating in Italy are genetically stable and, on the other hand, evidenced a continuous WNV circulation in Italy throughout the year. In this report case, a bird-to-bird WNV transmission was suggested to support the virus overwintering. The potential transmission through the oral route in a predatory bird may explain the relatively rapid spread of WNV, as well as other flaviviruses characterized by similar transmission patterns. However, rodent-to-bird transmission or mosquito-to-bird transmission cannot be excluded, and further research is needed to better understand WNV transmission routes during the winter season in Italy.

| S-EPMC9414329 | biostudies-literature

Putative new lineage of west nile virus, Spain.

Project description:To ascertain the presence of West Nile virus (WNV), we sampled mosquitoes in 2006 in locations in southern Spain where humans had been infected. WNV genomic RNA was detected in 1 pool from unfed female Culex pipiens mosquitoes. Phylogenetic analysis demonstrated that this sequence cannot be assigned to previously described lineages of WNV.

| S-EPMC3322021 | biostudies-literature

Introductions of West Nile virus strains to Mexico.

Project description:Complete genome sequencing of 22 West Nile virus isolates suggested 2 independent introductions into Mexico. A previously identified mouse-attenuated glycosylation variant was introduced into southern Mexico through the southeastern United States, while a common US genotype appears to have been introduced incrementally into northern Mexico through the southwestern United States.

| S-EPMC3373085 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data