A. Tishon et al., A MODEL OF MEASLES VIRUS-INDUCED IMMUNOSUPPRESSION - ENHANCED SUSCEPTIBILITY OF NEONATAL HUMAN PBLS, Nature medicine, 2(11), 1996, pp. 1250-1254
Citations number
33
Categorie Soggetti
Medicine, Research & Experimental",Biology,"Cell Biology
Measles virus (MV) still incites one of the most contagious infections
of humankind. Despite the development and use of an excellent live at
tenuated virus vaccine, over one million infants and children continue
to die each year from measles(1-3). The main cause of morbidity and m
ortality is virus-induced immunosuppression of lymphocyte function, wh
ich allows secondary infections. Here we report an in vivo model for t
he study of MV-induced immunosuppression. Human peripheral blood leuko
cytes (PBLs) grafted onto mice with severe combined immunodeficiency d
isease (SCID mice) to create hu-PBLS-SCID mice produce human IgG that
is suppressed by MV infection. Immunosuppression is dependent on the i
nvolvement of live virus and is dramatically more severe for PBLs obta
ined from newborns than PBLs from adults. Suppression of IgG synthesis
by PBLs from newborns occurs as early as ten days after administratio
n of MV to hu-PBLS-SCID mice compared with 44 days required for PBLs f
rom adults. Further, MV infection of SCID mice reconstituted with PBLs
from newborns reduces IgG production 26+/-5-fold (mean+/-1 s.e.m.) as
compared with only a 6+/-0.5-fold reduction in adults. MV RNA could b
e detected in live human PBLs recovered from SCID mice as long as 110
days after MV infection began. The profound immunosuppression we obser
ve in PBLs from infants probably contributes to the morbidity and mort
ality observed in infants vaccinated with measles virus. Further, this
model should be useful for accessing the potential immunosuppressive
abilities of newly isolated field (wildtype) virus isolates and newly
designed vaccines containing attenuated MV or subunit vaccines, as wel
l as in dissecting the role played by maternal antibodies to MV on the
ability of the virus to enhance or abort the virus-induced immunosupp
ression.