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• W2022291234 abstract "ABSTRACT Infection of mice with pneumonia virus of mice (PVM) provides a convenient experimental pathogenesis model in a natural host for a human respiratory syncytial virus-related virus. Extending our previous work showing that the PVM nonstructural (NS) proteins were pathogenicity factors in mice, we identify both the NS1 and NS2 proteins as antagonists of alpha/beta interferon (IFN-α/β) and IFN-λ by use of recombinant PVM (rPVM) with single and combined deletions of the NS proteins (ΔNS1, ΔNS2, and ΔNS1 ΔNS2). Wild-type and NS deletion PVMs were evaluated for growth and pathogenesis by infecting knockout mice that lack functional receptors to IFN-α/β, IFN-λ, or both. The absence of the receptor to IFN-α/β (IFNAR) or IFN-λ (interleukin-28 receptor α chain [IL-28Rα]) individually did not reverse the attenuated virulence of the NS deletion viruses although loss of IFNAR partially restored replication efficiency. When both receptors were deleted, replication and virulence were largely rescued for rPVM ΔNS1 and were significantly but not completely rescued for rPVM ΔNS2. As for rPVM ΔNS1 ΔNS2, the effect was mostly limited to partial enhancement of replication. This indicates that both IFN-α/β and IFN-λ contributed to restricting the NS deletion viruses, with the former playing the greater role. Interestingly, the replication and virulence of wild-type PVM were completely unaffected by the presence or absence of functional receptors to IFN-α/β and IFN-λ, indicating that both systems are strongly suppressed during infection. However, pretreatment of mice with IFN-α/β was protective against lethal rPVM challenge, whereas pretreatment with IFN-λ delayed but did not prevent disease and, in some cases, reduced mortality. The fact that virulence of rPVM lacking NS2 was not recovered completely when both interferon receptors were deleted suggests that NS2 may have further functions outside the IFN system." @default.
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• W2022291234 date "2011-05-01" @default.
• W2022291234 modified "2023-10-16" @default.
• W2022291234 title "Both Nonstructural Proteins NS1 and NS2 of Pneumonia Virus of Mice are Inhibitors of the Interferon Type I and Type III Responses In Vivo" @default.
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• W2022291234 doi "https://doi.org/10.1128/jvi.01365-10" @default.
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