Pathogenesis of nonimmune hydrops fetalis caused by intrauterine B19 infection.
Intrauterine human parvovirus B19 infection is related to non-immune hydrops fetalis and fetal death. First, we performed epidemiological studies to determine the critical period during which maternal infection led to hydrops fetalis. The studies showed that the hepatic period of hematopoietic activity was correlated with the critical period of maternal infection, which suggested that B19 might have affinity for erythroid lineage cells at the stage of hematopoiesis. We next established an in vitro infection experimental system of B19 using erythroid lineage cells derived from fetal liver cells. We demonstrated that the erythroid lineage cells proved to be appropriate targets for B19 virus and that B19 infection could induce apoptosis of infected cells. The massive destruction of erythroid lineage cells through apoptosis seems to cause severe anemia and to result in heart failure of the fetus. To analyze the cytotoxic mechanism in more detail, we established a stringent regulatory expression system of the NS1 protein encoded by the B19 genome and indicated that the apoptosis induced by B19 was directly caused by the NS1 protein. Experiments using mutations engineered in the ATP-binding domain of NS1 indicated that this domain played a critical role for the apoptosis induction. The present studies may contribute to a better understanding of the pathogenesis of hydrops fetalis associated with B19 infection during pregnancy.
Yaegashi
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Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan. nyaegashi@gonryo.med.tohoku.ac.jp
D000914:Antibodies, Viral / Q000032:analysis; D017209:Apoptosis; D004912:Erythrocytes / Q000821:virology; D005260:Female; D006801:Humans; D015160:Hydrops Fetalis / Q000209:etiology*; D018445:Infectious Disease Transmission, Vertical; D010322:Parvoviridae Infections / Q000150:complications* / Q000635:transmission; D016732:Parvovirus B19, Human / Q000472:pathogenicity* / Q000502:physiology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D017361:Viral Nonstructural Proteins / Q000502:physiology
D000914:Antibodies, Viral; C106202:NS1 protein, parvovirus; D017361:Viral Nonstructural Proteins