Our data are consistent with anterograde HeV entry into the brain, possibly via olfactory sensory neurons (OSN). Viral antigen was detected in both the olfactory mucosa and the olfactory bulbs of intranasally challenged mice as early as day 6 post infection and these two structures are connected by olfactory sensory neurons (OSN). OSNs are located within the olfactory mucosa of the nasal cavity and project cilia out into the lumen of the nasal cavity to detect odorants [27] . Their axons project to the olfactory bulb of the brain [28] and thereby provide pathogens with a potential route of direct transmission from the nasal cavity to the brain. Within the olfactory bulbs OSNs synapse with mitral, tufted (projection neurons) and peri/juxtaglomerular cells (interneurons) in the glomeruli [29] , and secondary dendrites of the mitral and tufted cells synapse with dendrites of granule cells, which reside largely in the granule cell layer [30] . The trigeminal nerve may provide another possible route of neuroinvasion from the nasal cavity to the glomeruli of the olfactory bulbs. Peripheral peptidergic fibres of the trigeminal nerve innervate the olfactory epithelium and at least some of these fibres will send collaterals to the olfactory bulb (fibres terminate in the glomeruli) [31] en route to the trigeminal ganglion and the contribution of these fibres to viral invasion of the olfactory bulbs requires closer investigation. Viral antigen and lesions were also identified in the pons and medulla in four mice. We suggest that in these cases brain infection occurred via another peripheral neural pathway that enters the CNS at the brainstem such as the trigeminal [27] or the vestibulocochlear nerve [32] and it is of interest that in one animal antigen was localised to the vestibular nuclei of the medulla, which would be consistent with neuroinvasion of the vestibulocochlear nerve [32] after infection arising in the inner ear.