VIRUS BEHAVIOUR AND DIVERSITY
In a 2008 HeV outbreak at an equine veterinary practice, equine cases presented with pronounced neurological signs, at odds with the predominantly respiratory presentations in previous outbreaks (Field et al.
2010). Experimental studies in mice have shown encephalitic disease can develop following neuro-invasion along sensory neurones, suggesting that route of infection may be a primary determinant of clinical presentation in horses (Dups et al. 2012). Notably, experimental inoculation of horses with the 2008 outbreak isolate showing that the virus strain did not affect clinical presentation (Marsh et al. 2011). Indeed, isolates from equine cases and flyingfox populations showed low genomic variation over space and time (Marsh et al. 2010; Smith et al. 2011). Multiple HeV variants (within the HeV-g1 group) were circulating in flying-fox populations at multiple locations at any time and, at times, the same variant was found circulating at disparate locations. This work concluded that spillover is not associated with particular HeV isolates, and that various host and/or environmental factors are likely the primary determinants of bat-horse spillover (expanded on in Plowright et al. 2015).In 2021, a novel variant of HeV (genotype 2, HeV-g2) was detected as the cause of death of a horse that died in 2015 (Annand et al. 2022). This horse had shown clinical signs suggestive of HeV disease but tested negative to HeV diagnostic assays at the time. Subsequent screening using broad pan-paramyxovirus PCRs identified a variant with sufficient sequence mismatches to avoid detection with routinely used diagnostic assays (Annand et al. 2022). This variant was 99% similar to sequences recovered from tissue samples from grey-headed flying-foxes, P. poliocephalus in 2013 and 2019-2021 (Wang et al. 2021). Following the update of diagnostic assays to ensure detection of all known variants, a second equine HeV-g2 spillover was detected in the Newcastle region in 2021 (Taylor et al.
2022). With detections in flying-foxes in SA, Vic., NSW, Qld and NT, HeV-g2 appears to be circulating in flying-foxes across a broad geographic range, albeit at lower apparent frequencies than HeV-g1 (Wang et al. 2021; Peel et al. 2022). Despite the sequence differences, HeV-g2 uses the same host receptor as HeV-g1 (Ephrin B2) and is effectively cross-neutralised by HeV-g1 neutralising antibodies (Wang et al. 2022).Given that the Ephrin B2 receptor is highly conserved in mammals, the potential host range for HeV is expected to be broad (Bonaparte et al. 2005). Evidence of natural HeV infection in dogs has been found on equine case properties (Kirkland et al. 2015), and although experimental studies showed that HeV was not highly pathogenic for dogs, virus was repeatedly isolated from the oral cavity of infected dogs, posing a potential transmission risk to in-contact humans (Middleton et al. 2017). Successful experimental infections have been established in several other species (Geisbert et al. 2012).
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