Impact and Regulation of Lambda Interferon Response in Human Metapneumovirus Infection

Human metapneumovirus (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 unknown. 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-lambda 1), IFN-lambda 2, IFN-lambda 3, and IFN-lambda 4. The induction of IFN-lambda expression by hMPV was dependent on interferon regulatory factor 7 (IRF-7) expression but not on IRF-3 expression. Treatment of hMPV-infected mice with IFN-lambda reduced the disease severity, lung viral titer, and inflammatory response in the lung. Moreover, the IFN-lambda response induced by the virus was regulated by the expression of the hMPV G protein. These results show that type III interferons (IFN-lambda s) play a critical protective role in hMPV infection. IMPORTANCE Human metapneumovirus (hMPV) is a pathogen of worldwide importance. Despite the relevance of hMPV as a pathogen, critical aspects of the immune response induced by this virus remain unidentified. Interferons (IFNs), including IFN-lambda, the newest addition to the interferon family, constitute an indispensable part of the innate immune response. Here, we demonstrated that IFN-lambda exhibited a protective role in hMPV infection in vitro and in an experimental mouse model of infection.