Distinct Roles of Interferon Alpha and Beta in Controlling Chikungunya Virus Replication and Modulating Neutrophil-Mediated Inflammation

• DOI: 10.1128/jvi.00841-19
• Publication Date: 2019-10-14T11:13:48Z
• Authors: Lindsey E. Cook; Marissa C. Locke; Alissa R. Young; Kristen Monte; Matthew L. Hedberg; Raeann M. Shimak; Kathleen C. F. Sh...; Deborah J. Veis; Michael S. Diamond; Deborah J. Lenschow
• Keywords: BETA (programming language); Alpha (finance); Alphavirus infection; Interferon type I

Type I interferons (IFNs) are key mediators of the innate immune response. Although members this family cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type IFNs essential control infection by chikungunya virus (CHIKV), globally emerging alphavirus, contributions individual subtypes remain undefined. To address question, we evaluated CHIKV pathogenesis mice lacking IFN-β (IFN-β knockout [IFN-β-KO] or treated with an IFN-β-blocking antibody) IFN-α (IFN regulatory factor 7 [IRF7-KO] pan-IFN-α-blocking antibody). Mice either developed severe clinical disease following CHIKV, marked increase foot swelling compared wild-type mice. Virological analysis revealed sustained elevated infected ankle distant tissues. In contrast, IFN-β-KO displayed minimal differences viral burdens within at distal sites instead had altered cellular increased neutrophil infiltration into musculoskeletal tissues, depletion neutrophils but not IRF7-KO mitigated caused CHIKV. Our findings suggest disparate roles for during infection, limiting early replication dissemination modulating neutrophil-mediated inflammation.IMPORTANCE possess range biological activity protect against number viruses, including alphaviruses. Despite signaling there established among The significance our research is demonstrating both have protective acute (CHIKV) do so distinct mechanisms. limits dissemination, whereas protects from inflammation mediated neutrophils. support premise activities antiviral