Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice

G. Grant Welstead, Caterina Iorio, Ryan Draker, Jane Bayani, Jeremy Squire, Sompong Vongpunsawad, Roberto Cattaneo, Christopher D. Richardson

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

A transgenic mouse containing the complete human SLAM (hSLAM/CD150) gene, including its endogenous promoter for transcription, was generated by using human genomic DNA cloned into a bacterial artificial chromosome. hSLAM, the primary receptor for measles viruses (MV), was expressed on activated B, T, and dendritic cells with an expression profile equivalent to that of humans. We demonstrated that hSLAM+ cells obtained from the transgenic mouse, including activated B, T, and dendritic cells, were susceptible to MV infection in a receptor-dependent manner. Evidence was provided for transient infection in the nasal lymph nodes of HSLAM+ mice after intranasal inoculation. Virus was rapidly cleared without signs of secondary replication. To improve the efficiency of MV production, the hSLAM+ mice were bred with mice having a Stat1-deficient background. These mice were more susceptible to MV infection and produced more virus particles. After intranasal and intraperitoneal inoculation of these mice with MV, infections of the thymus, spleen, nasal, mesenteric, and leg lymph nodes were detected. Upon necropsy, enlarged lymph nodes and spleen were apparent. Flow cytometric analysis showed that abnormally large numbers of mature neutrophils and natural killer cells caused the splenomegaly. The hSLAM transgenic mouse constitutes an improved rodent model for studying the interaction of MV with immune cells that more accurately reflects the infection pattern found in humans.

Original languageEnglish (US)
Pages (from-to)16415-16420
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number45
DOIs
StatePublished - Nov 8 2005

Keywords

  • Activated lymphocytes
  • Dendritic cells
  • Transgenic mouse

ASJC Scopus subject areas

  • General

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