Experimental West Nile Virus Infection in Rabbits:  An Alternative Model for Studying Induction of Disease  and Virus Control

Suen, Willy W.; Uddin, Muhammad Jasim; Wang, Wenqi; Brown, Vienna R.; Adney, Danielle R.; Broad, Nicole; Prow, Natalie A.; Bowen, Richard A.; Hall, Roy A.; Bielefeldt‐Ohmann, Helle

doi:10.3390/pathogens4030529

Cited by 19 publications

(59 citation statements)

References 68 publications

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“…When challenged with the highly virulent and closely related Murray Valley encephalitis virus (MVEV) or the North American WNV strain, WNV TX8667 , a similar resistant phenotype was observed in all infected NZWRs and CTRs, respectively [263]. While all rabbits were asymptomatic following virus challenge, we observed varying degrees of neuropathology and virus dissemination to lymphoid tissues [263].…”

Section: Introductionmentioning

confidence: 71%

“…While all rabbits were asymptomatic following virus challenge, we observed varying degrees of neuropathology and virus dissemination to lymphoid tissues [263]. The preliminary assessment of type I and II interferon (IFN-I/II) gene transcription in the draining popliteal lymph node (dPLN) and brain of WNV NSW2011 -and MVEV-infected weanling NZWRs (wNZWRs) suggested a different transcription pattern of cytokine genes between these two groups, which may explain the different kinetics of neutralising antibody production, the extent of systemic virus dissemination and neuropathology observed [263].…”

Section: Introductionmentioning

confidence: 86%

“…Infections can range from asymptomatic infections to self-resolving febrile disease to more severe, but mostly non-lethal neuroinvasive disease [210,271,272]. We have recently established a non-lethal WNV infection model in rabbits [263]. None of the New Zealand white (NZWR) and cottontail (CTR) rabbits infected with the Australian WNV strain of intermediate virulence, WNV NSW2011 , succumbed to the virus challenge, regardless of age or species of the rabbits [263].…”

Section: Introductionmentioning

confidence: 99%

“…We have recently established a non-lethal WNV infection model in rabbits [263]. None of the New Zealand white (NZWR) and cottontail (CTR) rabbits infected with the Australian WNV strain of intermediate virulence, WNV NSW2011 , succumbed to the virus challenge, regardless of age or species of the rabbits [263]. We had chosen NZWRs and CTRs for the comparison, since we were interested in the susceptibility profile of rabbits from different genetic and environmental background to infection with this recently isolated outbreak strain [263].…”

Section: Introductionmentioning

confidence: 99%

“…We characterised the transcription kinetics of selected pivotal inflammatory genes in the dPLN, non-draining popliteal lymph node (ndPLN), spleen, and brain of WNV NSW2011 -infected NZWRs and CTRs from the previous study [263]. Comparative transcription profiles were characterised in MVEVinfected NZWRs and WNV TX8667 -infected CTRs.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of neuropathogenesis and control of an equine-pathogenic Australian West Nile virus isolate in an established CD1 Swiss white mouse and a novel rabbit model

Suen¹

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West Nile virus (WNV) is a globally significant mosquito-borne neurotropic virus. In 2011, a large-scale arboviral encephalitis outbreak occurred in Australia, involving close to 1000 horses. A virulent WNV strain, WNV NSW2011 , was isolated from the brain of an encephalitic horse during this outbreak. Preliminary assessment showed that this strain is intermediate in virulence and belongs in the same lineage as the highly virulent North American strains. However, the pathogenesis of WNV in general, let alone this novel Australian strain, remains largely unclear.The first part of the project aimed to investigate the pathogenesis of lethal WNV NSW2011 infection in the established young adult Swiss white (CD1) mouse model, since previous survival challenge experiments demonstrated high lethality (~70%) of WNV NSW2011 in this animal model. I conducted a pilot time-course experiment, which demonstrated only benign pathological and virological outcomes in sacrificed mice on day 3 and 7 post-infection (pi), despite the relatively high lethality seen in previous survival trials. In a subsequent experiment, I characterised the disease phenotype in moribund/dead and surviving mice after WNV NSW2011 infection. Notably, I detected a high degree of intra-group variability in the neuropathology, neural infection and glial cell activation. Even cases with neuroinvasion are typically not fatal, unless underlying co-morbidities or immunosuppressive disease exist.I chose rabbits as a candidate for a novel animal model, due to the ease of performing intra-vital sampling and monitoring, as well as the possibility for tissue sharing in different assays, given the larger size of rabbits than mice. Rabbits are also hind-gut fermenters, and thus may be a better representation of a horse than a mouse. New Zealand White (NZWRs; Oryctolagus cuniculus) and iii North American cottontail rabbits (CTRs; Sylvilagus sp.) were challenged with WNV strains of different virulence (WNV NSW2011 and WNV TX8667 ), and the prototype Murray Valley encephalitis virus strain (MVE 1-51 ), by the footpad route. The rabbits were consistently resistant to developing severe disease after virulent WNV and MVEV infection, regardless of age, gender and species, despite productive virus replication in the draining popliteal lymph node (PLN). The resultant viraemia for all rabbits was also of low magnitude and transient. Furthermore, establishment of virus infection in the brain was not a feature of the disease, despite mild to moderate neuropathology in a subset of rabbits. This capacity to control flavivirus infection may be explained by the rapid antiviral innate immune response detectable by day 3 pi, as well as a fast anti-WNV neutralising antibody response detectable from day 7 pi.Comparisons of the tissue-specific transcriptional profile of important cytokine and chemokine genes suggested that virus control in rabbits was achieved differently depending on the virus, as well as the rabbit species. However, common transcriptional upregulation of IFNγ in...

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Section: Introductionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 86%