The Biological and Biochemical Pathogenesis of Mumps Virus-induced Embryonic Growth Retardation

Abstract

ExtractGrowth retardation in the mumps virus-infected chicken model is not due to a reduction in cell number but appears to Embryonic mumps virus infection in the avian host leads to be caused by a diminution in cell size. fetal growth retardation. The mechanism of this retardation has not been established.The avian host is unique in that the direct effect of a virus Speculation On the may be ascertained in the absence of a The relation between embryonic mumps virus infection and placenta.myocarditis is supported by the findings of high titers of virus Using radioisotope labeling techniques, RNA, and throughout the incubation period. It is postulated that altered protein metabolism was investigated in tissues from infected cardiac function results in a state of hypofusion and a and control chickens. Metabolism in organ tissue cultivated in preferential effect is seen in the brain with consequent vitro and then infected was also studied using the same diminution of cell size rather than cell radioisotope techniques.At hatch, the mean body weight of eight experimental chickens infected with mumps virus early during embryonic incubation was significantly less than that of 19 controls. This lower weight was evident in the brain of the infected chickens. The brain and carcass contained decreased amounts of RNA and protein when compared with uninfected control chickens. The kidney was the only other organ in which the protein content in experimental chickens was less than in controls.There was no difference in the DNA content of organs from in ovo-infected and control chickens or organ tissues cultivated in vitro before infection with mumps virus. Similarly, measurements of cell number at the same time were equal. Viral assay of the chickens infected in ovo revealed highest titers of virus in the heart throughout the last half of incubation. Intermediate titers of virus were recovered from 'the lung, spleen, and skeletal muscle. Low quantities of virus were recovered from the brain and liver. The bursa contained high titers of virus at midincubatio~ but these titers rapidly declined by hatch.Embryonic growth retardation has been attributed to many factors, including metabolic defects (lo), malnutrition of fetal and maternal origin (20, 24, 25, 32), congenital anomalies (3, 21), and infection (1,2,26). Under normal conditions the embryo grows as the population and size of cells increase. Conditions which impair either cellular variable will result in growth retardation. Several experimental models of fetal growth retardation in the mammal have been particularly illuminating. Wigglesworth (3 1 ) and Emmanouilides e t al. (9) ligated the uterine and umbilical arteries of the rat and sheep, respectively, producing placental insufficiency which resulted in fetal growth retardation.The avian model offers the opportunity for unique experimentation in that the direct effect of a virus on the chicken embryo may be ascertained in the absence of a placenta. Previous work has demonstrated that mumps virus infection during early ...

Induction of Abnormal Immunoglobulin Maturation and Antibody Production by Persistent Embryonic Mumps Virus Infection

“…The major consequence of embryonic viral infection is the inability of IgM-producing cells to switch to IgG synthesis. Mumps virus can be recovered from several embryonic organs throughout the last half of incubation (29). Although highest titers of virus are found in the heart, at midembryonic incubation the bursa of Fabricius also -infection may cause direct suppression of Ig transition by reorientation of cellular metabolism such that nucleic acid synthesis perquisite to normal Ig and antibody production is either impaired or an abnormal transcript is made.…”

“…In our model, embryonically infected bursal cells might instead synthesize a substance which represses differentiation of the more primitive stem cell, or blocks the production of the stem cell stimulator or hormone. Growth retardation occurs in chickens embryonically infected with mumps virus (24,27) and has been attributed to a diminution in the cell size of organs (29). During the full post-hatch period of these immunologic studies, experimental chickens were smaller than control birds.…”

“…Although highest titers of virus are found in the heart, at midembryonic incubation the bursa of Fabricius also -infection may cause direct suppression of Ig transition by reorientation of cellular metabolism such that nucleic acid synthesis perquisite to normal Ig and antibody production is either impaired or an abnormal transcript is made. Bursa1 cells cultivated from previously infected 12-day-old embryos demonstrate an increased metabolic rate as measured by incorporation of radiolabeled precursors (29), coinciding with the imitation of Ig synthesis in ovum (3). This metabolic alteration is unique to the bursa, since other organs are unaffected.…”

“…control host results in abnormal immunoglobulin maturation and antibody embryos hatched i n greater numbers and 2.-4 dozen embryos per production. The following mechanisms may influence the immune experiment generally produced an equal number of surviving response in this experimental model: viral replication may directly chickens (29). suppress the transition of IgM-producing cells within the embryonic and hatchling bursa at the stem cell level by altering genetic HEMAGGLUTIN IN ASSAY expression; infection may induce the production of a bursal repressor which disturbs the transition of immunoglobulin synthesis At 19 days of age, hatchling chickens were inoculated intramusfrom IgM to IgC; growth retardation may be associated with cularly in the right thigh with I ml 5% guinea pig erythrocytes generalized diminution of immunocellular replication and function.…”