Human Parvovirus B19 Nonstructural Protein 1 Regulates GATA1 Expression via the Notch Signaling Pathway in K562 Cell Line.

BACKGROUND: Human parvovirus B19 (B19) infection can affect the hematopoietic arrest in fetus by hindering the differentiation and maturation of erythroid progenitor cells. B19 nonstructural protein 1 (NS1) has been shown to inhibit the differentiation of erythroid progenitor cells. The goal of this study is to explore the role of B19 NS1 in the regulation of GATA1 and Notch signaling pathway in hematopoietic cells. METHODS: The B19 NS1 expression plasmid was reconstituted, and the possibility of NS1 regulating GATA1 and GATA2 expression modulated by Notch-Hes pathway was tested by qRT-PCR and western blot. Immunofluorescence assays were conducted to visualize pNS1 in K562 cells. RESULTS: We demonstrate that B19 NS1 inhibited GATA1 and induced Hes1/Hes5, which is involved in the activation of Notch signaling pathway. Meanwhile, NS1 exhibited promoting effects on GATA2 expression. Activation of the Notch signaling pathway up-regulated its downstream transcriptional repressor family Hes, thereby inhibiting the expression of GATA gene in K562 cells. CONCLUSIONS: The results show that B19 NS1 protein negatively regulates GATA1 related nuclear transcription and may interfere with hematopoietic cell differentiation.

New Insights of Human Parvovirus B19 in Modulating Erythroid Progenitor Cell Differentiation.

Human parvovirus B19 (B19), a human pathogen of the erythroparvovirus genus, is responsible for a variety of diseases. B19 cause less symptoms in healthy individuals, also cause acute and chronic anemia in immunodeficiency patients. Transient aplastic crisis and pure red cell aplasia are two kinds of anemic hemogram, respectively, in acute and chronic B19 infection phase, especially occurring in patients with a shortened red cell survival or with immunodeficiency. In addition, B19-infected pregnant women may cause hydrops fetalis or fetal loss. B19 possesses high affinity to bone marrow and fetal liver due to its extremely restricted cytotoxicity to erythroid progenitor cells (EPCs) mediated by viral proteins. The nonstructural protein NS1 is considered to be the major pathogenic factor, which has been shown to inhibit the differentiation and maturation of EPCs through inducing viral DNA damage responses and cell cycle arrest. The time phase property of NS1 activity during DNA replication and conformity to transient change of hemogram are suggestive of its role in regulating differentiation of hematopoietic cells, which is not completely understood. In this review, we summarized the bridge between B19 NS1 and Notch signaling pathway or transcriptional factors GATA, which play an important role in erythroid cell proliferation and differentiation, to provide a new insight of the potential mechanism of B19-induced differential inhibition of EPCs.

MicroRNAs: Mediators and Therapeutic Targets to Airway Hyper Reactivity After Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is the most important pathogen correlated to the first-time infant wheezing and later recurrence after its primary infection. RSV infection promotes the bronchial smooth muscle sensitivity to leukotrienes (LTs) in acute stage, causes the extensive inflammatory reaction and the aggregation of Th2-like cells during respiratory tract obstruction. Infants and young children infected with RSV exhibit an increased susceptibility to the exposure of exogenous allergens, easy to suffer from the recurrent wheezing, which prompts that the body is still in a state of inflammation or immunological bias. However, the pathological mechanism is unclear. The recent researches demonstrate that abnormal expression of non-coding microRNAs (miRNAs) can be detected from the peripheral blood and airway tract epithelial of RSV infected infants, which participate the regulation of immune cells polarization and LTs synthesis. Improving the immune tolerance can significantly relieve the airway inflammation and broncho-spasm caused by RSV. In this review, we discuss recent advances in understanding the mechanism of RSV-induced inflammatory reaction and immune dysfunction leading to airway hyper-reactivity. Further, we summarize the potential molecular basis that, in this process, miRNAs, which are produced by airway epithelial cells or peripheral blood mononuclear cells, directly or in the form of exosome to regulate the inflammation programs as well as the function, differentiation and proliferation of immune cells. miRNAs may become a potential bio-marker of detecting severe RSV infection and a novel target of early intervention and therapeutic strategy in recurrent wheezing or asthma related to RSV infection.