Parvovirus B19 genome as a single, two-state replicative and transcriptional unit

Bonvicini, Francesca; Filippone, Claudia; Delbarba, Stefania; Manaresi, Elisabetta; Zerbini, Marialuisa; Musiani, Monica; Gallinella, Giorgio

doi:10.1016/j.virol.2005.12.014

Cited by 28 publications

(34 citation statements)

References 26 publications

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“…In contrast, dimerreplicative intermediate forms of DNA did not appear until more than 16 hpi after infection. More recently, a more precise reevaluation of the expression profile of B19V genome in different cell types was obtained by means of quantitative PCR analysis, first assessing the relative abundance of distinct regions of the viral genome within the mRNA complement [105], and then by using a redundant PCR array to determine the relative frequency of the diverse species of mRNAs [106].…”

Section: Expression Profilementioning

confidence: 99%

Parvovirus B19 Achievements and Challenges

Gallinella

2013

ISRN Virology

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Parvovirus B19 is a widespread human pathogenic virus, member of the Erythrovirus genus in the Parvoviridae family. Infection can be associated with an ample range of pathologies and clinical manifestations, whose characteristics and outcomes depend on the interplay between the pathogenetic potential of the virus, its adaptation to different cellular environments, and the physiological and immune status of the infected individuals. The scope of this review is the advances in knowledge on the biological characteristics of the virus and of virus-host relationships; in particular, the interactions of the virus with different cellular environments in terms of tropism and ability to achieve a productive replicative cycle, or, on the contrary, to establish persistence; the consequences of infection in terms of interference with the cell physiology; the process of recognition of the virus by the innate or adaptive immune system, hence the role of the immune system in controlling the infection or in the development of clinical manifestations. Linked to these issues is the continuous effort to develop better diagnostic algorithms and methods and the need for development of prophylactic and therapeutic options for B19V infections.

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Section: Expression Profilementioning

confidence: 99%

Parvovirus B19 Achievements and Challenges

Gallinella

2013

ISRN Virology

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“…More about the B19V tropism has been learned from the fact that in addition to the native target cells for B19V infection in human bone marrow and fetal livers, a few cell lines (the megakaryoblastoid cell line UT7/Epo-S1 [31] and the erythroid leukemic cell line KU812Ep6 [28]) support B19V rep-lication, albeit at a limited efficiency (7,56). Recently, ex vivoexpanded CD36…”

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Role of Erythropoietin Receptor Signaling in Parvovirus B19 Replication in Human Erythroid Progenitor Cells

Chen

Guan

Lou

et al. 2010

J Virol

123

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Parvovirus B19 (B19V) infection is highly restricted to human erythroid progenitor cells. Although previous studies have led to the theory that the basis of this tropism is receptor expression, this has been questioned by more recent observation. In the study reported here, we have investigated the basis of this tropism, and a potential role of erythropoietin (Epo) that EpoR signaling is absolutely required for B19V replication in ex vivo-expanded erythroid progenitor cells after initial virus entry and at least partly accounts for the remarkable tropism of B19V infection for human erythroid progenitors.Parvovirus B19 (B19V) is pathogenic to humans. It replicates autonomously and belongs to the genus Erythrovirus in the family Parvoviridae (14). Clinical manifestations of B19V infection vary among different health conditions. The most common manifestation is erythema infectiosum. However, B19V infection often results in bone marrow failure under the following conditions (9, 10, 62). In patients with increased destruction of erythrocytes and a high turnover of erythrocytes (e.g., sickle cell disease patients), acute B19V infection can cause transient aplastic crisis. In immunocompromised patients, persistent B19V infection may develop manifestations as pure red-cell aplasia, a chronic anemia. Moreover, B19V fetal infection can cause severe anemia in the fetus, resulting in nonimmune hydrops fetalis and fetal death (1,2,16,47,57).Erythropoiesis is the process whereby a fraction of primitive multipotent hematopoietic stem cells (CD34 ϩ ) commit to the erythroid lineage, forming burst-forming units-erythroid (BFU-E; earlier erythroid progenitor) cells, CFU-erythroid (CFU-E; later erythroid progenitor) cells, normoblasts, erythroblasts, reticulocytes, and ultimately, mature erythrocytes. B19V infection shows a remarkable tropism for BFU-E and CFU-E progenitors in human bone marrow and fetal livers. Notably, both cell types express the cell surface marker CD36 (30,39,50,60). The clinical manifestations of B19V infection seen in both aplastic crisis and pure red-cell aplasia are direct outcomes of cell death of the erythroid progenitors that are targets of B19V replication, and this cell death is due to direct cytotoxicity of the virus infection (9, 13). Progressive host cell apoptosis has been observed during B19V infection of erythroid progenitor cells (29,49,60), and this is likely induced during infection of the abundantly expressed 11-kDa nonstructural protein of the virus (12). Apoptosis of erythroid progenitor cells is also characteristic of B19V-induced hydrops fetalis (60).Polyadenylation at the proximal site [(pA)p], which is located in the center of the B19V genome, precludes the inclusion of the capsid-encoding open reading frame (ORF) in transcripts under some conditions (38,61). We have recently shown that replication of the B19V genome enhances readthrough of the (pA)p and, thereafter, the polyadenylation of B19V transcripts at the distal site. Therefore, replication of the B19V genome facilitates the p...

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“…are the erythrocyte precursors CFU-E and BFU-E (26,37). A few semipermissive myeloblastoid cell lines have been isolated (e.g., UT7/Epo-S1 [20] and KU812Ep6 [18]) and support B19V infection with a limited efficiency (only a 10-fold increase of B19V genomes) (3,44). CD36…”

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Block to the Production of Full-Length B19 Virus Transcripts by Internal Polyadenylation Is Overcome by Replication of the Viral Genome

Guan

Cheng

Yoto

et al. 2008

J Virol

113

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The pre-mRNA processing strategy of the B19 virus is unique among parvoviruses. B19 virus-generated pre-mRNAs are transcribed from a single promoter and are extensively processed by alternative splicing and alternative polyadenylation to generate 12 transcripts. Blockage of the production of full-length B19 virus transcripts at the internal polyadenylation site [(pA)p] was previously reported to be a limiting step in B19 virus permissiveness. We show here that in the absence of genome replication, internal polyadenylation of B19 virus RNAs at (pA)p is favored in cells which are both permissive and nonpermissive for B19 viral replication. The human parvovirus B19 virus (B19V) is a member of the Erythrovirus genus in the subfamily Parvoviridae (8, 41). B19V causes a number of human diseases, such as fifth disease in children, arthropathy, particularly in women, transient aplastic crisis in individuals with a high red cell turnover rate, pure red cell aplasia in immunocompromised patients, and hydrops fetalis following infection of pregnant women (4).The B19V virion is approximately 20 nm in diameter and contains a single-stranded DNA genome of either plus or minus polarity. The left-hand portion of the genome contains the NS-encoding region, which is essential for virus replication, transcription transactivation, and cytotoxicity. The right-hand portion harbors the sequences for the two structural proteins, VP1 and VP2. At least 12 transcripts are generated by alternative splicing and alternative polyadenylation from a single pre-mRNA that is transcribed from the single promoter at map unit 6 (P6) (Fig. 1) (24, 46). B19V transcripts polyadenylated at the proximal polyadenylation site [(pA)p] accumulate as either spliced or unspliced mRNAs. As unspliced mRNAs, they encode the nonstructural NS1 protein, which is essential for virus replication. Spliced RNAs polyadenylated internally at (pA)p encode a 7.5-kDa protein whose function is unknown. All B19V transcripts detected so far that are polyadenylated at the distal polyadenylation site [(pA)d] excise the first intron (D1 to A1-1 or D1 to A1-2) (Fig. 1). Those that are not additionally spliced encode the capsid protein VP1. RNAs in which the second intron (D2 to A2-1) is additionally spliced encode the capsid protein VP2, while those additionally spliced between D2 and A2-2 encode the nonstructural 11-kDa protein that is essential for virus export from the nuclei (38, 48). Two internal polyadenylation sites, (pA)p1 and (pA)p2, have been identified. (pA)p1, which accounts for approximately 90% of the internal polyadenylation events, has a noncanonical cleavage and polyadenylation specificity factor binding motif (AUUAAA) located at nucleotide (nt) 2819. (pA)p2, which accounts for approximately 10% of the internal polyadenylation events, has a canonical signal of AAUAAA located at nt 3115 (46). B19V has been shown to undergo productive replication in erythroid progenitors of human hematopoietic stem cells (26,37). Different disease manifestations are due to the direct...

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Parvovirus B19 genome as a single, two-state replicative and transcriptional unit

Cited by 28 publications

References 26 publications

Parvovirus B19 Achievements and Challenges

Parvovirus B19 Achievements and Challenges

Role of Erythropoietin Receptor Signaling in Parvovirus B19 Replication in Human Erythroid Progenitor Cells

Block to the Production of Full-Length B19 Virus Transcripts by Internal Polyadenylation Is Overcome by Replication of the Viral Genome

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