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(1-3). 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 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 be detected in live human PBLs recovered from SCID mice as long as 110 days after MV infection began. The profound immunosuppression we observe in PBLs from infants probably contributes to the morbidity and mortality 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 well as in dissecting the role played by maternal antibodies to MV on the ability of the virus to enhance or abort the virus-induced immunosuppression.