West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms
| Autor: | Stanley A. Langevin, Payal D. Maharaj, Aaron C. Brault, Richard A. Bowen, Claire Y.-H. Huang, Richard M. Kinney, Elizabeth A. Dietrich, Mark J. Delorey |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
RNA viruses Viral Diseases Physiology viruses Pathogenesis Viral Nonstructural Proteins medicine.disease_cause Virus Replication Body Temperature 0302 clinical medicine Pathology and laboratory medicine Genetics Mutation Virulence Strain (biology) lcsh:Public aspects of medicine Temperature virus diseases Medical microbiology Phenotype Infectious Diseases Physiological Parameters Viruses Vertebrates Pathogens West Nile virus Research Article lcsh:Arctic medicine. Tropical medicine lcsh:RC955-962 030231 tropical medicine Viremia Biology Research and Analysis Methods Microbiology Birds 03 medical and health sciences Virology medicine Animals Point Mutation Molecular Biology Techniques Molecular Biology Medicine and health sciences NS3 Polymorphism Genetic Biology and life sciences Flaviviruses Bird Diseases Point mutation Public Health Environmental and Occupational Health Organisms Viral pathogens lcsh:RA1-1270 medicine.disease Kenya Viral Replication Microbial pathogens 030104 developmental biology Viral replication Amniotes North America West Nile Fever Cloning |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 10, Iss 8, p e0004938 (2016) |
| ISSN: | 1935-2735 1935-2727 |
| Popis: | West Nile virus (WNV) replicates in a wide variety of avian species, which serve as reservoir and amplification hosts. WNV strains isolated in North America, such as the prototype strain NY99, elicit a highly pathogenic response in certain avian species, notably American crows (AMCRs; Corvus brachyrhynchos). In contrast, a closely related strain, KN3829, isolated in Kenya, exhibits a low viremic response with limited mortality in AMCRs. Previous work has associated the difference in pathogenicity primarily with a single amino acid mutation at position 249 in the helicase domain of the NS3 protein. The NY99 strain encodes a proline residue at this position, while KN3829 encodes a threonine. Introduction of an NS3-T249P mutation in the KN3829 genetic background significantly increased virulence and mortality; however, peak viremia and mortality were lower than those of NY99. In order to elucidate the viral genetic basis for phenotype variations exclusive of the NS3-249 polymorphism, chimeric NY99/KN3829 viruses were created. We show herein that differences in the NS1-2B region contribute to avian pathogenicity in a manner that is independent of and additive with the NS3-249 mutation. Additionally, NS1-2B residues were found to alter temperature sensitivity when grown in avian cells. Author Summary West Nile virus (WNV) is a mosquito-borne virus that has caused outbreaks in humans in many regions of the world. Birds are the natural hosts for WNV. However, different strains of WNV cause different disease outcomes in birds. Here, we compared two WNV strains, one of which causes higher mortality and generates more virus in American crows than the other. Previous research has shown that this difference is due in large part to a difference between the two strains at a single amino acid in the NS3 gene; however, this difference does not completely explain the observed effect. Here we show that another region of the viral genome also affects disease outcomes in American crows, and changes the sensitivity of the virus to temperature when grown in bird cells. These findings help us to understand the genetic features that affect WNV infection and disease outcomes in its natural host. Detection of such features in new strains of WNV and related viruses could help to understand and predict future outbreaks. |
| Databáze: | OpenAIRE |
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