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Transcriptome of peripheral blood mononuclear cells in West Nile virus infection of horses and rabbits

Uddin, M.J., Suen, W.W., Bosco-Lauth, A., Hartwig, A-E, Hall, R.A., Bowen, R.A. and Bielefeldt-Ohmann, H. (2016) Transcriptome of peripheral blood mononuclear cells in West Nile virus infection of horses and rabbits. In: 11th International Veterinary Immunology Symposium 2016, 16 - 19 August 2016, Gold Coast Convention Centre, Queensland.


Following severe flooding in eastern Australia in 2011 an equine West Nile virus (WNV) induced encephalitis epidemic ensued with ~1000 horses affected and mortality of 10-15%. A new strain, WNVNSW2011 was isolated. Infections with WNV are mostly (>80%) mild to subclinical, likely because of a virus-limiting innate response in the peripheral blood leukocytes and draining lymph nodes. Therefore, we have investigated the transcripts of peripheral blood mononuclear cells (PBMCs) that might restrict the virus as the first line defence.

PBMCs were collected from intra-dermally WNVNSW2011-infected rabbits (n=12) and horses (n=3) on the day before infection (D-1), and various days post infection (DPI). Blood cells were also collected from control (n=3) rabbits and horses. Transcripts of interest including cytokines, Toll-like receptors (TLR), and TLR-associated downstream genes were quantified using quantitative RT- PCR.

Interferon α & β, IL6, IL22, CXCL10, PTX3, TLR1, TLR3, TLR6, STAT1, MyD88, TRAF3, IRF7, IRF9, IFIT2, and NOD2 mRNA expressions were upregulated on 1 DPI, and TLR3 and IRF3 remained highly upregulated till 3 DPI in rabbits. IFNα & β, IL22, PTX3, TLR7 mRNA expression was upregulated on days 1-7 DPI in horses. TLR1-3, TLR8 & TRAF3 mRNA expression was upregulated between 11-18 DPI, while MyD88, STST1, STAT2 & ISG15 mRNA expression was upregulated at 7 DPI in horses.

Both infection pathobiology in vivo, and transcriptome responses of PBMCs to WNV infection in vitro already established rabbit as an appropriate model for subclinical WNV-infection1-6. This study further showed that transcriptome kinetics of experimentally infected-rabbit PBMC were similar to that of horse cells. Furthermore, immediate recognition of virus by TLRs and rapid response of IFNs might be the limiting peripheral cellular factors contributing in subclinical features of the Australian WNV-strain.

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