A neonatal mouse model of Enterovirus D68 infection induces both interstitial pneumonia and acute flaccid myelitis

Abstract

Enterovirus D68 (EV-D68) is a causative agent of recent outbreaks of severe respiratory illness, pneumonia and acute flaccid myelitis (AFM) worldwide. The study of the pathogenesis, vaccines and anti-viral drugs for EV-D68 infection has been reported. Given the previously described mouse model of EV-D68, we sought to establish a neonatal mice model inducing both pneumonia and AFM. The neonatal BALB/c mice were inoculated intraperitoneally with the EV-D68 strain (named15296-virus) which was produced by the reverse genetics method. The infected mice displayed limb paralysis, tachypnea and even death, which were similar to the clinical symptoms of human infections. Moreover, the results of histopathologic examination and immunohistochemical staining showed acidophilic necrosis in the muscle, the spinal cord and alveolar wall thickening in the lung, indicating that EV-D68 exhibited strong tropism to the muscles, spinal cord and lung. Furthermore, the results of real-time PCR also suggested that the viral loads in the blood, spinal cord, muscles and lung were higher than those in other tissues at different time points post-infection. Additionally, the neonatal mouse model was used for evaluating the EV-D68 infection. The results of the anti-serum passive and maternal antibody protection indicated that the neonatal mice could be protected against the EV-D68 challenge, and displayed that both the serum of 15296-virus and prototype-virus (Fermon) were performing a certain cross-protective activity against the 15296-virus challenge. In summary, the above results proved that our neonatal mouse model possessed not only the interstitial pneumonia and AFM simultaneously but also a potentiality to evaluate the protective effects of EV-D68 vaccines and anti-viral drugs in the future.

Keywords: Acute flaccid myelitis; Enterovirus D68; Infection; Interstitial pneumonia; Neonatal mouse model.