Murine norovirus inhibits B cell development in the bone marrow of STAT1-deficient mice

Virology. 2018 Feb:515:123-133. doi: 10.1016/j.virol.2017.12.013. Epub 2017 Dec 26.

Abstract

Noroviruses are a leading cause of gastroenteritis in humans and it was recently revealed that noroviruses can infect B cells. We demonstrate that murine norovirus (MNV) infection can significantly impair B cell development in the bone marrow in a signal transducer and activator of transcription 1 (STAT1) dependent, but interferon signaling independent manner. We also show that MNV replication is more pronounced in the absence of STAT1 in ex vivo cultured B cells. Interestingly, using bone marrow transplantation studies, we found that impaired B cell development requires Stat1-/- hematopoietic cells and Stat1-/- stromal cells, and that the presence of wild-type hematopoietic or stromal cells was sufficient to restore normal development of Stat1-/- B cells. These results suggest that B cells normally restrain norovirus replication in a cell autonomous manner, and that wild-type STAT1 is required to protect B cell development during infection.

Keywords: B cells; B lymphocytes; Calicivirus; Murine norovirus; Norovirus; Stat1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / virology
  • Bone Marrow / metabolism*
  • Bone Marrow / virology
  • Caliciviridae Infections / metabolism*
  • Caliciviridae Infections / virology
  • Female
  • Gastroenteritis / metabolism*
  • Gastroenteritis / virology
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Norovirus / genetics
  • Norovirus / physiology*
  • STAT1 Transcription Factor / deficiency*
  • STAT1 Transcription Factor / genetics
  • Virus Replication

Substances

  • STAT1 Transcription Factor
  • Stat1 protein, mouse