Development of a cotton rat-human metapneumovirus (hMPV) model for identifying and evaluating potential hMPV antivirals and vaccines.

Hispid cotton rats were inoculated with two different human metapneumovirus (hMPV) subtype A strains and one subtype B hMPV. Although no overt disease was seen in any virus-inoculated animal, following an eclipse phase, significant pulmonary virus titers were observed in every hMPV-inoculated animal through day 7 post virus inoculation (p.i.) and in most through day 10. Peak virus titers occurred four days p.i., while virus-induced histopathology was most evident in lung sections obtained from animals 7 to 10 days p.i. The latter consisted primarily of desquamating and hypertrophic columnar epithelial cells lining the bronchi and bronchioles and the presence of large numbers of leukocytes in and around the bronchi and bronchioles. In fluorescent antibody studies, virus antigen-specific fluorescence was most evident in the desquamating tall columnar epithelial cells lining bronchi and bronchioles, in pneumocytes lining alveoli and in single or small groups of free cells, most probably leukocytes, present in the lumen of alveoli, bronchi and bronchioles. Virus was generally not detected in inoculated animals >10 days p.i. Although the pattern of virus replication in cotton rats was similar for all the three virus stains, the B subtype consistently grew to lower levels than the two A strains. Regardless, these findings indicate that hMPV replicates in cotton rats and that these animals may be used as a small animal model of hMPV infection and to facilitate the identification and development of vaccines and antivirals for preventing and/or ameliorating infections caused by this virus.