Impact and Regulation of Lambda Interferon Response in Human Metapneumovirus Infection

Humanmetapneumovirus (hMPV) is a respiratory paramyxovirus that is distributed worldwide and induces significant airway morbidity. Despite the relevance of hMPV as a pathogen, many aspects of the immune response to this virus are still largely un-known. In this report, we focus on the antiviral immune response, which is critical for viral clearance and disease resolution. Using in vitro and in vivo systems, we show that hMPV is able to induce expression of lambda interferon 1 (IFN-1), IFN-2, IFN-3, and IFN-4. The induction of IFN- expression by hMPVwas dependent on interferon regulatory factor 7 (IRF-7) ex-pression but not on IRF-3 expression. Treatment of hMPV-infected mice with IFN- reduced the disease severity, lung viral titer, and inflammatory response in the lung. Moreover, the IFN- response induced by the virus was regulated by the expression of the hMPVG protein. These results show that type III interferons (IFN-s) play a critical protective role in hMPV infection. IMPORTANCE Humanmetapneumovirus (hMPV) is a pathogen of worldwide importance. Despite the relevance of hMPV as a pathogen, criti-cal aspects of the immune response induced by this virus remain unidentified. Interferons (IFNs), including IFN-, the newest addition to the interferon family, constitute an indispensable part of the innate immune response. Here, we demonstrated that IFN- exhibited a protective role in hMPV infection in vitro and in an experimental mouse model of infection. Humanmetapneumovirus (hMPV) was first identified in 2001after its isolation from infants and children with lower respi