Poster Presentation 8th Australasian Virology Society Meeting and 11th Annual Meeting of the Australian Centre for Hepatitis & HIV Virology Meeting 2015

Tissue-specific transcriptional profile of cytokine and chemokine genes associated with West Nile virus control in a novel rabbit model (#201)

Willy W Suen 1 , Jasim Uddin 1 , Natalie Prow 2 3 , Richard A Bowen 4 , Roy Hall 2 5 , Helle Bielefeldt-Ohmann 1 2 5
  1. School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia
  2. Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, QLD, Australia
  3. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  4. Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA
  5. School of Chemistry and Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia

Most equine and human West Nile virus (WNV) infections are non-lethal. Yet, little is known about the mechanisms by which these species overcome virulent WNV infection.   The incomplete resistance of mice to virulent WNV infection has limited its suitability to study virus control.  We have previously shown that New Zealand White (NZWRs) and cottontail (CTRs) rabbits are consistently resistant to severe disease development after intradermal infection with WNV and Murray Valley encephalitis virus (MVEV).  Establishment of productive virus infection in the brain was not observed, despite virus replication in the draining popliteal lymph node (PLN).  The current study aims to identify the temporal- and tissue-specific pattern of cytokine/chemokine gene transcription, associated with virus control in WNV- and MVEV-infected rabbits.  We characterized the transcriptional profile of IFNα, IFNβ, IFNγ, TNFα, IL6, IL4, CXCL10, and IL10 genes in the brain, spleen, draining and non-draining PLN.

The transcriptional pattern of these genes varied for the virus and rabbit species.  In particular, MVEV infection in weanling NZWRs induced significantly higher levels of IFNα, TNFα, IL6 and CXCL10 transcripts in the brain on day 12 pi, relative to WNVNSW2011.  This correlated with the difference in neuropathology between these two groups.  Furthermore, CTRs achieved virus control without acute upregulation of several cytokine/chemokine transcripts, contrary to NZWRs.  This suggests a distinct virus control mechanism in CTRs.  Despite these differences, we observed common acute upregulation of IFNγ transcript in the draining PLN, which may be associated with local control of virus replication.  Early IL10 mRNA upregulation was detected in most tissues of NZWRs, suggesting that early regulation of the inflammatory response is important for appropriate virus control without excessive inflammation in this species.  Thus, this study has shown that, in rabbits, virus control is achieved via different mechanisms depending on virus and host factors.