Persistence of Systemic Murine Norovirus Is Maintained by Inflammatory Recruitment of Susceptible Myeloid Cells

Jacob A. Van Winkle, Bridget A. Robinson, A. Mack Peters, Lena Li, Ruth V. Nouboussi, Matthias Mack, Timothy J. Nice

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Viral persistence can contribute to chronic disease and promote virus dissemination. Prior work demonstrated that timely clearance of systemic murine norovirus (MNV) infection depends on cell-intrinsic type I interferon responses and adaptive immunity. We now find that the capsid of the systemically replicating MNV strain CW3 promotes lytic cell death, release of interleukin-1α, and increased inflammatory cytokine release. Correspondingly, inflammatory monocytes and neutrophils are recruited to sites of infection in a CW3-capsid-dependent manner. Recruited monocytes and neutrophils are subsequently infected, representing a majority of infected cells in vivo. Systemic depletion of inflammatory monocytes or neutrophils from persistently infected Rag1−/− mice reduces viral titers in a tissue-specific manner. These data indicate that the CW3 capsid facilitates lytic cell death, inflammation, and recruitment of susceptible cells to promote persistence. Infection of continuously recruited inflammatory cells may be a mechanism of persistence broadly utilized by lytic viruses incapable of establishing latency. Persistence of continuously replicating RNA viruses, such as murine norovirus (MNV), requires a maintained reservoir of infected cells. Van Winkle et al. find that the MNV capsid directs systemic persistence by dictating the host inflammatory environment through promotion of cell lysis and the sustained recruitment of MNV susceptible myeloid cells.

Original languageEnglish (US)
Pages (from-to)665-676.e4
JournalCell Host and Microbe
Volume24
Issue number5
DOIs
StatePublished - Nov 14 2018

Keywords

  • inflammation
  • monocytes
  • neutrophils
  • norovirus
  • persistence

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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