Impact and regulation of lambda interferon response in human metapneumovirus infection

Authors

Ma Del Baños-Lara, Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
Lindsey Harvey, Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
Alexander Mendoza, Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
Dawn Simms, Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
Vladimir N. Chouljenko, Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA Center for Experimental Infectious Disease Research, Louisiana State University, Baton Rouge, Louisiana, USA.
Nobuko Wakamatsu, Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
K Gus Kousoulas, Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA Center for Experimental Infectious Disease Research, Louisiana State University, Baton Rouge, Louisiana, USA.
Antonieta Guerrero-Plata, Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA Center for Experimental Infectious Disease Research, Louisiana State University, Baton Rouge, Louisiana, USA aguerrp@lsu.edu.

Document Type

Article

Publication Date

1-1-2015

Abstract

UNLABELLED: 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-λ1), IFN-λ2, IFN-λ3, and IFN-λ4. The induction of IFN-λ 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-λ reduced the disease severity, lung viral titer, and inflammatory response in the lung. Moreover, the IFN-λ response induced by the virus was regulated by the expression of the hMPV G protein. These results show that type III interferons (IFN-λs) 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-λ, the newest addition to the interferon family, constitute an indispensable part of the innate immune response. Here, we demonstrated that IFN-λ exhibited a protective role in hMPV infection in vitro and in an experimental mouse model of infection.

Publication Source (Journal or Book title)

Journal of virology

First Page

730

Last Page

42

Recommended Citation

Baños-Lara, M. D., Harvey, L., Mendoza, A., Simms, D., Chouljenko, V. N., Wakamatsu, N., Kousoulas, K. G., & Guerrero-Plata, A. (2015). Impact and regulation of lambda interferon response in human metapneumovirus infection. Journal of virology, 89 (1), 730-42. https://doi.org/10.1128/JVI.02897-14