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Role of type I interferon signaling in human metapneumovirus pathogenesis and control of viral replication.

Authors
  • Hastings, Andrew K
  • Erickson, John J
  • Schuster, Jennifer E
  • Boyd, Kelli L
  • Tollefson, Sharon J
  • Johnson, Monika
  • Gilchuk, Pavlo
  • Joyce, Sebastian
  • Williams, John V
Type
Published Article
Journal
Journal of Virology
Publisher
American Society for Microbiology
Publication Date
Apr 01, 2015
Volume
89
Issue
8
Pages
4405–4420
Identifiers
DOI: 10.1128/JVI.03275-14
PMID: 25653440
Source
Medline
License
Unknown

Abstract

Human metapneumovirus (HMPV) is a leading cause of acute respiratory illness. CD8(+) T cells are critical for clearing viral infection, yet recent evidence shows that HMPV and other respiratory viruses induce CD8(+) T cell impairment via PD-1-PD-L1 signaling. We sought to understand the role of type I interferon (IFN) in the innate and adaptive immune responses to HMPV by using a mouse model lacking IFN signaling. Although HMPV titers were higher in the absence of type I IFN, virus was nonetheless cleared and mice were less ill, indicating that type I IFN is not required to resolve HMPV infection but contributes to pathogenesis. Further, despite lower levels of the inhibitory ligand PD-L1 in mice lacking type I IFN, CD8(+) T cells were more impaired in these mice than in WT mice. Our data suggest that specific antigen-presenting cell subsets and the inhibitory receptor Tim-3 may contribute to CD8(+) T cell impairment.

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