The West Nile-like flavivirus Koutango is highly virulent in mice due to delayed viral clearance and the induction of a poor neutralizing antibody response

Prow, Natalie A., Setoh, Yin X., Biron, Rebecca M., Sester, David P., Kim, Kwang Sik, Hobson-Peters, Jody, Hall, Roy A. and Bielefeldt-Ohmann, Helle (2014) The West Nile-like flavivirus Koutango is highly virulent in mice due to delayed viral clearance and the induction of a poor neutralizing antibody response. Journal of Virology, 88 17: 9947-9962. doi:10.1128/JVI.01304-14


Author Prow, Natalie A.
Setoh, Yin X.
Biron, Rebecca M.
Sester, David P.
Kim, Kwang Sik
Hobson-Peters, Jody
Hall, Roy A.
Bielefeldt-Ohmann, Helle
Title The West Nile-like flavivirus Koutango is highly virulent in mice due to delayed viral clearance and the induction of a poor neutralizing antibody response
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
1070-6321
Publication date 2014-09
Year available 2014
Sub-type Article (original research)
DOI 10.1128/JVI.01304-14
Open Access Status DOI
Volume 88
Issue 17
Start page 9947
End page 9962
Total pages 16
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2015
Language eng
Formatted abstract
The mosquito-borne West Nile virus (WNV) is responsible for outbreaks of viral encephalitis in humans, horses and birds with particularly virulent strains causing recent outbreaks of disease in Eastern Europe, the Middle East, North America and Australia. Previous studies have phylogenetically separated WNV strains into two main genetic lineages (I and II), containing virulent strains associated with neurological disease. Several WNV-like strains, clustering outside these lineages have been identified and form an additional five proposed lineages. However, little is known about whether these strains have the potential to induce disease. In a comparative analysis with the highly virulent Lineage I American strain (WNVNY99), the low pathogenic Lineage II strain (B956) and a benign Australian strain, Kunjin (WNVKUN); the African WNV-like Koutango virus (WNVKOU) and a WNV-like isolate from Sarawak, Malaysia (WNVSarawak) were assessed for neuroinvasive properties in a murine model and for their replication kinetics in vitro. While WNVNY99 replicated to highest levels in vitro, in vivo mouse challenge revealed that WNVKOU was more virulent with a shorter time to onset of neurological disease and higher morbidity. Histological analysis of WNVKOU- and WNVNY99-infected brain and spinal cords demonstrated a more prominent meningoencephalitis and presence of viral antigen in WNVKOU-infected mice. Enhanced virulence of WNVKOU was also associated with poor viral clearance in the periphery (sera and spleen), a skewed innate immune response and poor neutralizing antibody development. These data demonstrate for the first time potent neuroinvasive and neurovirulent properties of a WNV-like virus outside of Lineage I and II.

Importance In this study, we characterized the in vitro and in vivo properties of previously uncharacterized West Nile virus strains and West Nile-like viruses. We identified a West Nile-like virus, Koutango (WNVKOU) that was more virulent than a known virulent Lineage 1 virus, (WNVNY99). Enhanced virulence of WNVKOU was associated with poor viral clearance and the induction of a poor neutralization antibody response. These findings provide new insights into the pathogenesis of West Nile virus.
Keyword West Nile virus
Neuroinvasion
Virulence
Pathogenesis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 18 June 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
School of Veterinary Science Publications
 
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Created: Fri, 27 Jun 2014, 14:48:49 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences