Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice.
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.
Welstead
G Grant
GG
Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON, Canada M5C 2C8.
Iorio
Caterina
C
Draker
Ryan
R
Bayani
Jane
J
Squire
Jeremy
J
Vongpunsawad
Sompong
S
Cattaneo
Roberto
R
Richardson
Christopher D
CD
D000818:Animals; D015703:Antigens, CD; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D007136:Immunoglobulins / Q000235:genetics / Q000502:physiology*; D008214:Lymphocytes / Q000821:virology*; D008459:Measles virus / Q000276:immunology / Q000502:physiology*; D051916:Membrane Cofactor Protein / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface; D050794:STAT1 Transcription Factor / Q000502:physiology; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014779:Virus Replication
D015703:Antigens, CD; D006023:Glycoproteins; D007136:Immunoglobulins; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1