Dataset Information

Complete Genome Sequence of West Nile Virus (WNV) from the First Human Case of Neuroinvasive WNV Infection in Cyprus.

ABSTRACT: We report here the complete genome sequence of a West Nile virus (WNV) strain from the first laboratory-confirmed human case of neuroinvasive WNV infection in Cyprus. Phylogenetic analysis showed that this WNV strain grouped clearly into genetic lineage 1, clade 1a, cluster 2.

SUBMITTER: Richter J

PROVIDER: S-EPMC5658487 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Complete Genome Sequence of West Nile Virus (WNV) from the First Human Case of Neuroinvasive WNV Infection in Cyprus.

Richter Jan J Tryfonos Christina C Tourvas Aristomenis A Floridou Dora D Paphitou Niki I NI Christodoulou Christina C

Genome announcements 20171026 43

We report here the complete genome sequence of a West Nile virus (WNV) strain from the first laboratory-confirmed human case of neuroinvasive WNV infection in Cyprus. Phylogenetic analysis showed that this WNV strain grouped clearly into genetic lineage 1, clade 1a, cluster 2. ...[more]

PMID: 29074649

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Project description:BackgroundWest Nile Virus (WNV) is a flavivirus that requires an efficient humoral and cellular host response for the control of neuroinvasive infection. We previously reported the existence of six alternative open reading frame proteins in WNV genome, one of which entitled WARF4 is exclusively restricted to the lineage I of the virus. WARF4 is able to elicit antibodies in WNV infected horses; however, there was no direct experimental proof of the existence of this novel protein. The purpose of this study was to demonstrate the in vitro production of WARF4 protein following WNV infection of cultured VERO cells and its immunity in WNV infected individuals.ResultsWe produced a monoclonal antibody against WARF4 protein (MAb 3A12) which detected the novel protein in WNV lineage I-infected, cultured VERO cells while it did not react with WNV lineage II infected cells. MAb 3A12 specificity to WARF4 protein was confirmed by its reactivity to only one peptide among four analyzed that cover the full WARF4 amino acids sequence. In addition, WARF4 protein was expressed in the late phase of WNV lineage I infection. Western blotting and bioinformatics analyses strongly suggest that the protein could be translated by programmed -1 ribosomal frameshifting process. Since WARF4 is embedded in the NS4B gene, we rename this novel protein N-NS4B/WARF4. Furthermore, serological analysis shows that N-NS4B/WARF4 is able to elicit antibodies in WNV infected individuals.ConclusionsN-NS4B/WARF4 is the second Alternative Reading Frame (ARF) protein that has been demonstrated to be produced following WNV infection and might represent a novel tool for a better characterization of immune response in WNV infected individuals. Further serological as well as functional studies are required to characterize the function of the N-NS4B/WARF4 protein. Since the virus might actually make an extensive use of ARFs, it appears important to investigate the novel six ARF putative proteins of WNV.

Project description:BackgroundWest Nile Virus (WNV) is a mosquito-borne flavivirus that has caused ongoing seasonal epidemics in the United States since 1999. It is estimated that ≤1% of WNV-infected patients will develop neuroinvasive disease (West Nile encephalitis and/or myelitis) that can result in debilitating morbidities and long-term sequelae. It is essential to collect longitudinal information about the recovery process and to characterize predicative factors that may assist in therapeutic decision-making in the future.MethodsWe report a longitudinal study of the neurological outcomes (as measured by neurological examination, Glascow Coma Scale, and Modified Mini-Mental State Examination) for 55 subjects with WNV neuroinvasive disease (confirmed by positive CSF IgM) assessed on day 7, at discharge, and on days 14, 30, and 90. The neurological outcome measures were coma (presence and degree), global cognitive status, presence of cranial neuropathy, tremors and/or weakness.ResultsAt initial clinical presentation 93% presented with a significant neurological deficit (49% with weakness, 35% with tremor, and 16% with cranial neuropathy). The number of patients with a cognitive deficit fell from 25 at initial evaluation to 9 at their last evaluation. Cranial neuropathy was present in 9 at onset and in only 4 patients at study conclusion. Of the 19 patients who had a tremor at enrollment, 11 continued to exhibit a tremor at follow-up. Seven patients died after initial enrollment in the study, with 5 of those having presented in a coma. The factors that predict either severity or long-term recovery of neurological function include age (older individuals were weaker at follow-up examination), gender (males recovered better from coma), and presentation in a coma with cranial nerve deficits (had a poorer recovery particularly with regard to cognition).ConclusionsThis study represents one of the largest clinical investigations providing prospectively-acquired neurological outcomes data among American patients with WNV central nervous system disease. The findings show that the factors that influence prognosis from the initial presentation include age, gender, and specific neurological deficits at onset.Trial registrationClinicalTrials.gov identifier: NCT00138463 and NCT00069316.

Dataset Information

Complete Genome Sequence of West Nile Virus (WNV) from the First Human Case of Neuroinvasive WNV Infection in Cyprus.

Publications

Complete Genome Sequence of West Nile Virus (WNV) from the First Human Case of Neuroinvasive WNV Infection in Cyprus.

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