A model of measles virus-induced immunosuppression: enhanced susceptibility of neonatal human PBLs.
Measles virus (MV) still incites one of the most contagious infections of humankind. Despite the development and use of an excellent live attenuated virus vaccine, over one million infants and children continue to die each year from measles. The main cause of morbidity and mortality is virus-induced immunosuppression of lymphocyte function, which allows secondary infections. Here we report an in vivo model for the study of MV-induced immunosuppression. Human peripheral blood leukocytes (PBLs) grafted onto mice with severe combined immunodeficiency disease (SCID mice) to create hu-PBLS-SCID mice produce human IgG that is suppressed by MV infection. Immunosuppression is dependent on the involvement of live virus and is dramatically more severe for PBLs obtained from newborns than PBLs from adults. Suppression of IgG synthesis by PBLs from newborns occurs as early as ten days after administration of MV to hu-PBLS-SCID mice compared with 44 days required for PBLs from adults. Further, MV infection of SCID mice reconstituted with PBLs from newborns.
Tishon
A
A
Scripps Research Institute, Department of Neuropharmacology, La Jolla, California 92037, USA.
Manchester
M
M
Scheiflinger
F
F
Oldstone
M B
MB
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001483:Base Sequence; D017690:Cell Transplantation; D017931:DNA Primers; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D008459:Measles virus / Q000235:genetics / Q000276:immunology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis
D015703:Antigens, CD; C497857:CD46 protein, human; D017931:DNA Primers; D007074:Immunoglobulin G; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D012367:RNA, Viral