Variability in IFN Secretion in Response to the Human Metapneumovirus CZ0107 Strain: A Comparative Study in BALB/c and C57BL/6 Mouse Models

The human metapneumovirus (HMPV) is a major respiratory pathogen mainly affecting infants under 5 years old. The interferon (IFN) response varies among patients, animal models, and HMPV strains, and this variation is crucial because the initial IFN response controls viral replication. Therefore, it is important to study the different profiles of IFN secretion during the same HMPV infection across various animal models. In this study, BALB/c and C57BL/6 mice were infected with a clinical A1 strain of HMPV-CZ0107, and at the endpoint, the expression of different types of IFN was measured. BALB/c mice showed significant weight loss and viral replication, while C57BL/6 mice exhibited notable neutrophil infiltration. Mice infected with BALB/c displayed significant secretion of all tested IFN types in all samples, whereas C57BL/6-infected mice showed significant secretion of IFN-α and IFN-γ only in the lungs. Additionally, infected BALB/c and C57BL/6 mice demonstrated different activation patterns of IFN-α- and IFN-γ-secreting natural killer (NK) cells, including both immature and mature cells. These findings characterize the IFN response induced by HMPV-CZ0107 and suggest that this infection results in higher secretion of IFNs in BALB/c mice compared to C57BL/6 mice, which may help explain the less severe clinical parameters observed in C57BL/6 mice.