To address the hypothesis that respiratory distress associated with West Nile virus (WNV) is neurologically caused, electromyographs (EMGs) were measured longitudinally from the diaphragms of alert hamsters infected subcutaneously (s.c.) with WNV. The EMG activity in WNV-infected hamsters was consistently and significantly (P <= .001) less than that of sham-infected animals, beginning with suppression at day 3 and continuing to beyond day 17 after viral challenge. Of the tissues known to affect respiration, i.e., lung, diaphragm, cervical spinal cord, brain stem, and the carotid or aortic bodies, foci of WNV-immunoreactive neurons were only observed in the brain stems and some cervical spinal cords from EMG-suppressed animals. To confirm the involvement of the brain stem and spinal cord, WNV was injected directly in the ventrolateral medulla containing respiratory functions using stereotaxic surgery and into the cervical cord at the C4 vertebral level. As with subcutaneous WNV challenge, hamsters developed EMG suppression of the diaphragm within 4 days. Because WNV-positive neurons were only sporadically identified in EMG-suppressed animals as early as day 3, a plausible mechanism of EMG suppression may involve regulation of diaphragm activity via vagal afferents acting on respiratory control system neurons in the brain stem. Brain auditory evoked response (BAER) was performed to determine if generalized brain stem neuropathy was the cause of diaphragmatic EMG suppression. Because deficiencies of BAER were only observed after day 11, which is long after diaphragm EMGs became suppressed, multiple phases of WNV-induced neurological disease are likely. These data establish that WNV infection of hamsters causes electrophysiological suppression of the diaphragm either directly by lesions in the brain stem and cervical spinal cord, or indirectly by altered vagal afferent function. This WNV-induced EMG suppression may be analogous to conditions leading to respiratory distress of WNV-infected human patients. Journal of NeuroVirology (2010) 16, 318-329.
