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

Nathan W. Bartlett, Karen Buttigieg, Sergei V. Kotenko, Geoffrey L. Smith

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

Human interferon lambdas (IFN-λs) (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-λs by recombinant vaccinia virus (VACV) is described and these proteins are shown to have potent antiviral activity in vivo. VACV expressing murine IFN-λ2 (vIFN-λ2) and IFN-λ3 (vIFN-λ3) showed normal growth in tissue culture and expressed N-glycosylated IFN-λ in infected cell extracts and culture supernatants. The role that murine IFN-λs play during virus infection was assessed in two different mouse models. vIFN-λ2 and vIFN-λ3 were avirulent for mice infected intranasally and induced no signs of illness or weight loss, in contrast to control viruses. Attenuation of vIFN-λ2 was associated with increases in lymphocytes in bronchial alveolar lavages and CD4+ T cells in total-lung lymphocyte preparations. In addition, vIFN-λ2 was cleared more rapidly from infected lungs and, in contrast to control viruses, did not disseminate to the brain. Expression of IFN-λ2 also attenuated VACV in an intradermal-infection model, characterized by a delay in lesion onset and reduced lesion size. Thus, by characterizing murine IFN-λs within a mouse infection model, the potent antiviral and immunostimulatory activity of IFN-λs in response to poxvirus infection has been demonstrated.

Original languageEnglish (US)
Pages (from-to)1589-1596
Number of pages8
JournalJournal of General Virology
Volume86
Issue number6
DOIs
StatePublished - Jun 2005

All Science Journal Classification (ASJC) codes

  • Virology

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