TY - JOUR
T1 - Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice
AU - Welstead, G. Grant
AU - Iorio, Caterina
AU - Draker, Ryan
AU - Bayani, Jane
AU - Squire, Jeremy
AU - Vongpunsawad, Sompong
AU - Cattaneo, Roberto
AU - Richardson, Christopher D.
PY - 2005/11/8
Y1 - 2005/11/8
N2 - 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.
AB - 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.
KW - Activated lymphocytes
KW - Dendritic cells
KW - Transgenic mouse
UR - http://www.scopus.com/inward/record.url?scp=28044464983&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28044464983&partnerID=8YFLogxK
U2 - 10.1073/pnas.0505945102
DO - 10.1073/pnas.0505945102
M3 - Article
C2 - 16260741
AN - SCOPUS:28044464983
SN - 0027-8424
VL - 102
SP - 16415
EP - 16420
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 45
ER -