Subcapsular sinus macrophages limit dissemination of West Nile virus particles after inoculation but are not essential for the development of West Nile virus-specific T cell responses

Evandro R. Winkelmann, Douglas G. Widman, Jingya Xia, Alison J. Johnson, Nico van Rooijen, Peter W. Mason, Nigel Bourne, Gregg N. Milligan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Macrophages encounter flaviviruses early after injection by arthropod vectors. Using in vivo imaging of mice inoculated with firefly luciferase-expressing single-cycle flavivirus particles (FLUC-SCFV), we examined the initial dissemination of virus particles in the presence or absence of lymph node (LN)-resident macrophages. Higher luciferase activity, indicating higher SCFV gene expression, was detected in the footpad of macrophage-depleted mice after 24h post infection (hpi). Moreover, FLUC-SCFV particles disseminated to the spleen within 14hpi in macrophage-depleted, but not control mice. Although macrophages presented SCFV to naïve T cells in vitro, depletion of subcapsular sinus (SCS) macrophages did not alter the magnitude or effector function of the WNV-specific CD8+ T cell response. Together, these results indicate that SCS macrophages play a role in limiting the dissemination of SCFV early in infection but are not required for the generation of a polyfunctional WNV-specific CD8+ T cell response in the draining LN.

Original languageEnglish (US)
Pages (from-to)278-289
Number of pages12
JournalVirology
Volume450-451
DOIs
StatePublished - Feb 2014

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West Nile virus
Virion
Macrophages
T-Lymphocytes
Flavivirus
Firefly Luciferases
Arthropod Vectors
Lymph Nodes
Infection
Luciferases
Spleen
Gene Expression
Injections

Keywords

  • CD8 T cell
  • RepliVAX
  • Single-cycle flavivirus
  • Subcapsular sinus macrophages
  • West Nile virus

ASJC Scopus subject areas

  • Virology

Cite this

Subcapsular sinus macrophages limit dissemination of West Nile virus particles after inoculation but are not essential for the development of West Nile virus-specific T cell responses. / Winkelmann, Evandro R.; Widman, Douglas G.; Xia, Jingya; Johnson, Alison J.; van Rooijen, Nico; Mason, Peter W.; Bourne, Nigel; Milligan, Gregg N.

In: Virology, Vol. 450-451, 02.2014, p. 278-289.

Research output: Contribution to journalArticle

Winkelmann, Evandro R. ; Widman, Douglas G. ; Xia, Jingya ; Johnson, Alison J. ; van Rooijen, Nico ; Mason, Peter W. ; Bourne, Nigel ; Milligan, Gregg N. / Subcapsular sinus macrophages limit dissemination of West Nile virus particles after inoculation but are not essential for the development of West Nile virus-specific T cell responses. In: Virology. 2014 ; Vol. 450-451. pp. 278-289.
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abstract = "Macrophages encounter flaviviruses early after injection by arthropod vectors. Using in vivo imaging of mice inoculated with firefly luciferase-expressing single-cycle flavivirus particles (FLUC-SCFV), we examined the initial dissemination of virus particles in the presence or absence of lymph node (LN)-resident macrophages. Higher luciferase activity, indicating higher SCFV gene expression, was detected in the footpad of macrophage-depleted mice after 24h post infection (hpi). Moreover, FLUC-SCFV particles disseminated to the spleen within 14hpi in macrophage-depleted, but not control mice. Although macrophages presented SCFV to na{\"i}ve T cells in vitro, depletion of subcapsular sinus (SCS) macrophages did not alter the magnitude or effector function of the WNV-specific CD8+ T cell response. Together, these results indicate that SCS macrophages play a role in limiting the dissemination of SCFV early in infection but are not required for the generation of a polyfunctional WNV-specific CD8+ T cell response in the draining LN.",
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