Measles virus infection of SLAM (CD150) knockin mice reproduces tropism and immunosuppression in human infection.
The human signaling lymphocyte activation molecule (SLAM, also called CD150), a regulator of antigen-driven T-cell responses and macrophage functions, acts as a cellular receptor for measles virus (MV), and its V domain is necessary and sufficient for receptor function. We report here the generation of SLAM knockin mice in which the V domain of mouse SLAM was replaced by that of human SLAM. The chimeric SLAM had an expected distribution and normal function in the knockin mice. Splenocytes from the SLAM knockin mice permitted the in vitro growth of a virulent MV strain but not that of the Edmonston vaccine strain. Unlike in vitro infection, MV could grow only in SLAM knockin mice that also lacked the type I interferon receptor (IFNAR). After intraperitoneal or intranasal inoculation, MV was detected in the spleen and lymph nodes throughout the body but not in the thymus. Notably, the virus appeared first in the mediastinal lymph node after intranasal inoculation. Splenocytes from MV-infected IFNAR(-/-) SLAM knockin mice showed suppression of proliferative responses to concanavalin A. Thus, MV infection of SLAM knockin mice reproduces lymphotropism and immunosuppression in human infection, serving as a useful small animal model for measles.
Ohno
Shinji
S
Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan. soono@virology.med.kyushu-u.ac.jp
Ono
Nobuyuki
N
Seki
Fumio
F
Takeda
Makoto
M
Kura
Shinobu
S
Tsuzuki
Teruhisa
T
Yanagi
Yusuke
Y
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D007165:Immunosuppression Therapy; D008198:Lymph Nodes / Q000821:virology; D008214:Lymphocytes / Q000276:immunology / Q000821:virology; D008457:Measles / Q000276:immunology*; D008459:Measles virus / Q000502:physiology*; D008482:Mediastinum; D051379:Mice / Q000235:genetics; D008822:Mice, Transgenic; D023421:Models, Animal; D017434:Protein Structure, Tertiary / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013154:Spleen / Q000821:virology; D014779:Virus Replication
D015703:Antigens, CD; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C000604059:SLAMF1 protein, human; D003208:Concanavalin A; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1