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

• Published in: Journal of general virology Vol. 86; no. 6; pp. 1589 - 1596
• Main Authors: Bartlett, Nathan W, Buttigieg, Karen, Kotenko, Sergei V, Smith, Geoffrey L
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.06.2005; Society for General Microbiology
• Subjects: Animals; Biological and medical sciences; Bronchoalveolar Lavage Fluid - immunology; CD4-Positive T-Lymphocytes - immunology; Cell Line; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Gene Expression; Interferons - biosynthesis; Interferons - genetics; Interferons - immunology; Interferons - pharmacology; Lymphocyte Count; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Molecular Sequence Data; Phylogeny; Poxviridae Infections - immunology; Poxviridae Infections - pathology; Poxvirus; Reassortant Viruses - immunology; Skin - pathology; Vaccinia virus; Vaccinia virus - immunology; Virology; Virus; Vertebrata; Mammalia; Microbiology; Mouse; Poxviridae; Rodentia; Antiviral; Interferon; Models; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.80904-0

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.