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Abstract

Human interferon lambdas (IFN-s) (type III IFNs) exhibit antiviral activity 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 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 . VACV expressing murine IFN-2 (vIFN-2) and IFN-3 (vIFN-3) showed normal growth in tissue culture and expressed -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.

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2005-06-01
2019-10-19
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vol. , part 6, pp. 1589 – 1596

Amino acid alignment of mouse IFN-λ2 and IFN-λ3 with the mouse type I and type II IFNs [PDF](112 KB)



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