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 Nice

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)665-676
Number of pages12
JournalCell host & microbe
Volume24
Issue number5
DOIs
StatePublished - Nov 14 2018

Fingerprint

Norovirus
Myeloid Cells
Capsid
Monocytes
Neutrophils
Cell Death
Infection
Viruses
Interferon Type I
Adaptive Immunity
Interleukin-1
Chronic Disease
Cytokines
Inflammation

Keywords

  • inflammation
  • monocytes
  • neutrophils
  • norovirus
  • persistence

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

Cite this

Persistence of Systemic Murine Norovirus Is Maintained by Inflammatory Recruitment of Susceptible Myeloid Cells. / Van Winkle, Jacob A.; Robinson, Bridget A.; Peters, A. Mack; Li, Lena; Nouboussi, Ruth V.; Mack, Matthias; Nice, Timothy.

In: Cell host & microbe, Vol. 24, No. 5, 14.11.2018, p. 665-676.

Research output: Contribution to journalArticle

Van Winkle, Jacob A. ; Robinson, Bridget A. ; Peters, A. Mack ; Li, Lena ; Nouboussi, Ruth V. ; Mack, Matthias ; Nice, Timothy. / Persistence of Systemic Murine Norovirus Is Maintained by Inflammatory Recruitment of Susceptible Myeloid Cells. In: Cell host & microbe. 2018 ; Vol. 24, No. 5. pp. 665-676.
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