Pathogenesis of Human Metapneumovirus Lung Infection in BALB/c Mice and Cotton Rats

Abstract

ABSTRACT Human metapneumovirus (hMPV) is a newly described member of the Paramyxoviridae family causing acute respiratory tract infections, especially in young children. We studied the pathogenesis of this viral infection in two experimental small animal models (BALB/c mice and cotton rats). Significant viral replication in the lungs of both animals was found following an intranasal challenge of 10 8 50% tissue culture infectious doses (TCID 50 ) and persisted for <2 and <3 weeks in the case of cotton rats and mice, respectively. Peak viral loads were found on day 5 postinfection in both mice (mean of 1.92 × 10 7 TCID 50 /g lung) and cotton rats (mean of 1.03 × 10 5 TCID 50 /g). Clinical symptoms consisting of breathing difficulties, ruffled fur, and weight loss were noted in mice only around the time of peak viral replication. Most significant pulmonary inflammatory changes and peak expression of macrophage inflammatory protein 1α, gamma interferon, and RANTES occurred at the time of maximal viral replication (day 5) in both models. Cellular infiltration occurred predominantly around and within alveoli and persisted for at least 21 days in mice, whereas it was more limited in time with more peribronchiolitis in cotton rats. Both animal models would be of great value in evaluating different therapeutic agents, as well as vaccine candidates against hMPV.