A cytotoxic nonstructural protein, NS1, of human parvovirus B19 induces activation of interleukin-6 gene expression.

1996 ◽  
Vol 70 (12) ◽  
pp. 8485-8491 ◽  
Author(s):  
S Moffatt ◽  
N Tanaka ◽  
K Tada ◽  
M Nose ◽  
M Nakamura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interleukin 6 ◽  
Nonstructural Protein ◽  
Parvovirus B19 ◽  
Human Parvovirus B19

scholarly journals Human Parvovirus B19 Nonstructural Protein (NS1) Induces Cell Cycle Arrest at G1 Phase

2003 ◽  
Vol 77 (5) ◽  
pp. 2915-2921 ◽  
Author(s):  
Eiji Morita ◽  
Akitoshi Nakashima ◽  
Hironobu Asao ◽  
Hiroyuki Sato ◽  
Kazuo Sugamura
Keyword(s):  
Cell Cycle ◽  
Virus Infection ◽  
Cell Cycle Arrest ◽  
Nonstructural Protein ◽  
Parvovirus B19 ◽  
Erythroid Cell ◽  
Human Parvovirus B19 ◽  
Cycle Arrest ◽  
Nonstructural Protein 1 ◽  
Ns1 Expression

ABSTRACT Human parvovirus B19 infects predominantly erythroid precursor cells, leading to inhibition of erythropoiesis. This erythroid cell damage is mediated by the viral nonstructural protein 1 (NS1) through an apoptotic mechanism. We previously demonstrated that B19 virus infection induces G2 arrest in erythroid UT7/Epo-S1 cells; however, the role of NS1 in regulating cell cycle arrest is unknown. In this report, by using paclitaxel, a mitotic inhibitor, we show that B19 virus infection induces not only G2 arrest but also G1 arrest. Interestingly, UV-irradiated B19 virus, which has inactivated the expression of NS1, still harbors the ability to induce G2 arrest but not G1 arrest. Furthermore, treatment with caffeine, a G2 checkpoint inhibitor, abrogated the B19 virus-induced G2 arrest despite expression of NS1. These results suggest that the B19 virus-induced G2 arrest is not mediated by NS1 expression. We also found that NS1-transfected UT7/Epo-S1 and 293T cells induced cell cycle arrest at the G1 phase. These results indicate that NS1 expression plays a critical role in G1 arrest induced by B19 virus. Furthermore, NS1 expression significantly increased p21/WAF1 expression, a cyclin-dependent kinase inhibitor that induces G1 arrest. Thus, G1 arrest mediated by NS1 may be a prerequisite for the apoptotic damage of erythroid progenitor cells upon B19 virus infection.

scholarly journals The Genome of Human Parvovirus B19 Can Replicate in Nonpermissive Cells with the Help of Adenovirus Genes and Produces Infectious Virus

2009 ◽  
Vol 83 (18) ◽  
pp. 9541-9553 ◽  
Author(s):  
Wuxiang Guan ◽  
Susan Wong ◽  
Ning Zhi ◽  
Jianming Qiu
Keyword(s):  
Nonstructural Protein ◽  
Parvovirus B19 ◽  
Leukemic Cell ◽  
Progeny Virus ◽  
Human Parvovirus B19 ◽  
Erythroid Progenitor ◽  
Leukemic Cell Lines ◽  
Nonstructural Protein 1 ◽  
293 Cells

ABSTRACT Human parvovirus B19 (B19V) is a member of the genus Erythrovirus in the family Parvoviridae. In vitro, autonomous B19V replication is limited to human erythroid progenitor cells and in a small number of erythropoietin-dependent human megakaryoblastoid and erythroid leukemic cell lines. Here we report that the failure of B19V DNA replication in nonpermissive 293 cells can be overcome by adenovirus infection. More specifically, the replication of B19V DNA in the 293 cells and the production of infectious progeny virus were made possible by the presence of the adenovirus E2a, E4orf6, and VA RNA genes that emerged during the transfection of the pHelper plasmid. Using this replication system, we identified the terminal resolution site and the nonstructural protein 1 (NS1) binding site on the right terminal palindrome of the viral genome, which is composed of a minimal origin of replication spanning 67 nucleotides. Plasmids or DNA fragments containing an NS1 expression cassette and this minimal origin were able to replicate in both pHelper-transfected 293 cells and B19V-semipermissive UT7/Epo-S1 cells. Our results have important implications for our understanding of native B19V infection.

Anti-human parvovirus B19 nonstructural protein antibodies in patients with rheumatoid arthritis

2009 ◽  
Vol 405 (1-2) ◽  
pp. 76-82 ◽  
Author(s):  
Bor-Show Tzang ◽  
Chun-Chou Tsai ◽  
Gregory J. Tsay ◽  
Meilin Wang ◽  
Yu-Shu Sun ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Nonstructural Protein ◽  
Parvovirus B19 ◽  
Human Parvovirus B19

scholarly journals Roles of E4orf6 and VA I RNA in Adenovirus-Mediated Stimulation of Human Parvovirus B19 DNA Replication and Structural Gene Expression

2012 ◽  
Vol 86 (9) ◽  
pp. 5099-5109 ◽  
Author(s):  
K. Winter ◽  
K. von Kietzell ◽  
R. Heilbronn ◽  
T. Pozzuto ◽  
H. Fechner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Structural Gene ◽  
Parvovirus B19 ◽  
Human Parvovirus B19 ◽  
Stimulation Of

scholarly journals The 11-Kilodalton Nonstructural Protein of Human Parvovirus B19 Facilitates Viral DNA Replication by Interacting with Grb2 through Its Proline-Rich Motifs

2018 ◽  
Vol 93 (1) ◽  
Author(s):  
Peng Xu ◽  
Aaron Yun Chen ◽  
Safder S. Ganaie ◽  
Fang Cheng ◽  
Weiran Shen ◽  
...  
Keyword(s):  
Dna Replication ◽  
Nonstructural Protein ◽  
Parvovirus B19 ◽  
Growth Factor Receptor ◽  
Cellular Growth ◽  
Human Parvovirus B19 ◽  
Nonstructural Proteins ◽  
Viral Dna ◽  
Viral Dna Replication

ABSTRACTLytic infection of human parvovirus B19 (B19V) takes place exclusively in human erythroid progenitor cells of bone marrow and fetal liver, which disrupts erythropoiesis. During infection, B19V expresses three nonstructural proteins (NS1, 11-kDa, and 7.5-kDa) and two structural proteins (VP1 and VP2). While NS1 is essential for B19V DNA replication, 11-kDa enhances viral DNA replication significantly. In this study, we confirmed the enhancement role of 11-kDa in viral DNA replication and elucidated the underlying mechanism. We found that 11-kDa specially interacts with cellular growth factor receptor-bound protein 2 (Grb2) during virus infection andin vitro. We determined a high affinity interaction between 11-kDa and Grb2 that has an equilibrium dissociation constant (KD) value of 18.13 nM.In vitro, one proline-rich motif was sufficient for 11-kDa to sustain a strong interaction with Grb2. In consistence,in vivoduring infection, one proline-rich motif was enough for 11-kDa to significantly reduce phosphorylation of extracellular signal-regulated kinase (ERK). Mutations of all three proline-rich motifs of 11-kDa abolished its capability to reduce ERK activity and, accordingly, decreased viral DNA replication. Transduction of a lentiviral vector encoding a short hairpin RNA (shRNA) targetingGrb2decreased the expression of Grb2 as well as the level of ERK phosphorylation, which resulted in an increase of B19V replication. These results, in concert, indicate that the B19V 11-kDa protein interacts with cellular Grb2 to downregulate ERK activity, which upregulates viral DNA replication.IMPORTANCEHuman parvovirus B19 (B19V) infection causes hematological disorders and is the leading cause of nonimmunological fetal hydrops during pregnancy. During infection, B19V expresses two structural proteins, VP1 and VP2, and three nonstructural proteins, NS1, 11-kDa, and 7.5-kDa. While NS1 is essential, 11-kDa plays an enhancing role in viral DNA replication. Here, we elucidated a mechanism underlying 11-kDa protein-regulated B19V DNA replication. 11-kDa is tightly associated with cellular growth factor receptor-bound protein 2 (Grb2) during infection.In vitro, 11-kDa interacts with Grb2 with high affinity through three proline-rich motifs, of which at least one is indispensable for the regulation of viral DNA replication. 11-kDa and Grb2 interaction disrupts extracellular signal-regulated kinase (ERK) signaling, which mediates upregulation of B19V replication. Thus, our study reveals a novel mechanism of how a parvoviral small nonstructural protein regulates viral DNA replication by interacting with a host protein that is predominately expressed in the cytoplasm.

scholarly journals Human parvovirus B19 nonstructural protein NS1 enhanced the expression of cleavage of 70kDa U1-snRNP autoantigen

2010 ◽  
Vol 17 (1) ◽  
pp. 40 ◽  
Author(s):  
Bor-Show Tzang ◽  
Der-Yuan Chen ◽  
Chun-Chou Tsai ◽  
Szu-Yi Chiang ◽  
Tsung-Ming Lin ◽  
...  
Keyword(s):  
Nonstructural Protein ◽  
Parvovirus B19 ◽  
Human Parvovirus B19 ◽  
U1 Snrnp

scholarly journals New Insights of Human Parvovirus B19 in Modulating Erythroid Progenitor Cells Differentiation

2019 ◽  
Author(s):  
Shuwen Feng ◽  
Dongxin Zeng ◽  
Junwen Zheng ◽  
Dongchi Zhao
Keyword(s):  
Progenitor Cells ◽  
Nonstructural Protein ◽  
Parvovirus B19 ◽  
Fetal Loss ◽  
Main Body ◽  
Severe Anemia ◽  
Red Cell ◽  
Human Parvovirus B19 ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

Background Human parvovirus B19, a human pathogen of the erythroparvovirus genus, is responsible for a variety of diseases. Despite less symptoms caused by B19 infection in healthy individuals, this pathogen can not be neglected in specific groups who exhibit severe anemia. Main body of abstract Transient aplastic crisis and pure red cell aplasia are two kinds of anemic hemogram respectively in acute phase and chronic B19 infection, especially occur in individuals with a shortened red cell survival or immunocompromised patients. In addition, B19 infected pregnant women may suffer risks of hydrops fetalis secondary to severe anemia and fetal loss. B19 possesses high affinity to bone marrow and fetal liver due to its extremely restricted cytotoxicity to erythroid progenitor cells mediated by viral proteins. The nonstructural protein NS1 is considered to be the major pathogenic factor, which takes parts in differentiational inhibition and apoptosis of erythroid progenitor cells 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. Conclusion In this review, we set up a hypothetic bridge between B19 NS1 and Notch signaling pathway or transcriptional factors GATA which are essential in hematopoiesis, to provide a new insight of the potential mechanism of B19-induced differentiational inhibition of erythroid progenitor cells.

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