Parvovirus B19 and the pathogenesis of anaemia.
Human parvovirus B19 (B19) infection causes human bone marrow failure, by affecting erythroid-lineage cells which are well-known target cells for B19. The anaemia induced by B19 infection is of minor clinical significance in healthy children and adults, however, it becomes critical in those afflicted with haemolytic diseases. This condition is called transient aplastic crisis, and the pathogenesis is explained by the short life-span of red blood cells. Similarly, fetuses are thought to be severely affected by B19-intrauterine infection in the first and second trimester, as the half-life of red blood cells is apparently shorter than RBC at the bone marrow haematopoietic stage. On the other hand, B19 is also the causative agent of persistent anaemia in immunocompromised patients, transplant recipients and infants. The deficiencies of appropriate immune responses to B19 impair viral elimination in vivo, which results in enlargement of B19-infected erythroid-lineage cells. The B19-associated damage of erythroid lineage cells is due to cytotoxicity mediated by viral proteins. B19-infected erythroid-lineage cells show apoptotic features, which are thought to be induced by the non-structural protein, NS1, of B19. In addition, B19 infection induces cell cycle arrests at the G(1) and G(2) phases. The G(1) arrest is induced by NS1 expression prior to apoptosis induction in B19-infected cells, while the G(2) arrest is induced not only by infectious B19 but also by UV-inactivated B19, which lacks the ability to express NS1. In this review, we address the clinical manifestations and molecular mechanisms for B19-induced anaemia in humans and a mouse model, and of B19-induced cell cycle arrests in erythroid cells.
Chisaka
Hiroshi
H
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Morita
Eiji
E
Yaegashi
Nobuo
N
Sugamura
Kazuo
K
D000328:Adult; D000740:Anemia / Q000276:immunology / Q000821:virology*; D017209:Apoptosis / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000821:virology; D002453:Cell Cycle / Q000276:immunology; D002648:Child; D015672:Erythroid Precursor Cells / Q000276:immunology / Q000821:virology; D004920:Erythropoiesis / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D010322:Parvoviridae Infections / Q000097:blood / Q000276:immunology / Q000821:virology*; D016732:Parvovirus B19, Human / Q000502:physiology*; D011247:Pregnancy; D017361:Viral Nonstructural Proteins / Q000276:immunology
C106202:NS1 protein, parvovirus; D017361:Viral Nonstructural Proteins