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Murine interferon lambdas (type III interferons) exhibit potent antiviral activity in vivo in a poxvirus infection model

Nathan W. Bartlett^1,

Karen Buttigieg^1,

¹ Department of Virology, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK
² Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, Newark, USA

Correspondence
Geoffrey L. Smith
glsmith{at}imperial.ac.uk

Human interferon lambdas (IFN-s) (type III IFNs) exhibit antiviral activity in vitro by binding to a receptor complex distinct from that used by type I and type II IFNs, and subsequent signalling through the Janus kinase signal transducers and activators of transcription (STAT) pathway. However, evidence for a function of type III IFNs during virus infection in vivo is lacking. Here, the expression of murine IFN-s by recombinant vaccinia virus (VACV) is described and these proteins are shown to have potent antiviral activity in vivo. VACV expressing murine IFN-2 (vIFN-2) and IFN-3 (vIFN-3) showed normal growth in tissue culture and expressed N-glycosylated IFN- in infected cell extracts and culture supernatants. The role that murine IFN-s play during virus infection was assessed in two different mouse models. vIFN-2 and vIFN-3 were avirulent for mice infected intranasally and induced no signs of illness or weight loss, in contrast to control viruses. Attenuation of vIFN-2 was associated with increases in lymphocytes in bronchial alveolar lavages and CD4⁺ T cells in total-lung lymphocyte preparations. In addition, vIFN-2 was cleared more rapidly from infected lungs and, in contrast to control viruses, did not disseminate to the brain. Expression of IFN-2 also attenuated VACV in an intradermal-infection model, characterized by a delay in lesion onset and reduced lesion size. Thus, by characterizing murine IFN-s within a mouse infection model, the potent antiviral and immunostimulatory activity of IFN-s in response to poxvirus infection has been demonstrated.

Published online ahead of print on 22 March 2005 as DOI 10.1099/vir.0.80904-0.

The GenBank/EMBL/DDBJ accession numbers for the sequences reported in this paper are AY869695 (129/Sv mouse IFN-2) and AY869696 (IFN-3).

An amino acid alignment of mouse IFN-2 and IFN-3 with the mouse type I and type II IFNs is available as supplementary material in JGV Online.

Present address: Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK.

Present address: Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berks RG20 7NN, UK.

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