Human lung epithelial cells support human metapneumovirus persistence by overtaking apoptosis

Human metapneumovirus (hMPV) has been identified as a major cause of lower respiratory tract infection in children. Epidemiological and molecular evidences highlighted an association between severe childhood respiratory viral infection and chronic lung diseases, as asthma and Chronic Obstructive Pulmonary Disease. Currently, animal models demonstrated the ability of hMPV to persist in vivo suggesting a role of virus in asthma development in children. However, mechanisms involved in hMPV persistence in the respiratory tract have not yet been understood. In the present study we monitored hMPV infection in the human alveolar epithelial cells A549 in order to understand if the virus is able to persist into these cells upon acute infection. Our data show that hMPV initially induces an apoptotic process in A549 cells through PARP-1 cleavage, caspase3/7 activation and Wee1 activity. Then, hMPV-infected cells became able to overtake the apoptotic pathway and cell cycle arrest in G2/M by expressing Bcl-2 and to acquire a reservoir cell phenotype with constant production of infectious virus. These findings provide evidence of the hMPV capability to persist in alveolar epithelial cells and help us in understanding the mechanisms responsible for hMPV persistence in the human respiratory tract.