Infection with measles virus induces a transient immunosuppression, which occasionally results in fatal opportunistic infections. To obtain fundamental information about the mechanism, we examined peripheral blood mononuclear cells (PBMC) from acute measles patients aged from infants to 35 years old, obtained at various times from incubation periods to 103 days after onset of rash, for the number of lymphocyte subsets by flowcytometry. The data were analyzed for relationships between aging of the patients and the severity of immunosuppression. In classical measles cases, infected lymphocytes detected as a minor population during the incubation period disappeared soon after onset of rash, whereas in the cases of serious illness, the infected cells persisted longer after the rash. At the onset of rash, remarkable lymphopenia had already occurred in all measles cases with reduction in cell numbers of CD4+ T cells, CD8+ T cells, B cells, neutrophils, and monocytes. In contrast, natural killer (NK) cells were increased in number and activated, which might be a response compensatory for the lymphopenia. Apoptosis-associated molecules such as CD95(Fas) and TNF-related apoptosis-inducing ligand-receptor (TRAIL-R) were highly expressed on the cell surface of most surviving non-infected lymphocytes, and DNA fragmentation was also observed upon incubation in vitro. These results suggested that the profound lymphopenia was primarily due to extended death of non-infected blood cells caused by apoptosis. The severity and duration of the lumphopenia were age-dependent; less severe in young children whereas much severer in infants under one year of age as well as adolescents and adults. From these results, it was suggested that remarkable lymphopenia due to apoptosis of uninfected cells is one of the principal causes for immunosuppression induced by measles virus infection, and is correlated with the age-dependent severity of the disease.
The processing of measles virus hemagglutinin glycoprotein (H) in infected cells was studied by pulse-chase method and two-dimensional isoelectric focusing and SDS-polyacrylamide slab gel electrophoresis. H glycoprotein was synthesized initially as polypeptides smaller than H glycoprotein present in the virions. They were then processed into a cohort of polypeptides of larger molecular size and with reduced charge. The change was associated with the expression of H glycoprotein on the cell surface. The removal of sialic acid from carbohydrate chain of H glycoprotein resulted in the shift of isoelectric point to a more basic range. The entire process of maturation of H glycoprotein required approximately 5 hours. Carbohydrate content in H was determined to be approximately 12 per cent by weight. Mannose, galactose, fucose, N-acetylglucosamine, and N-acetylneuraminic acid were the constituent monosaccharides.
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