NS1 Protein of Parvovirus B19 Interacts Directly with DNA Sequences of the p6 Promoter and with the Cellular Transcription Factors Sp1/Sp3

Raab, Ulla; Beckenlehner, Karin; Lowin, Torsten; Niller, Hans-Helmut; Doyle, Seán; Modrow, Susanne

doi:10.1006/viro.2001.1285

Cited by 83 publications

(61 citation statements)

References 35 publications

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“…Whereas B. mori DNV and C. extranea DNV have a restricted host range (B. mori and C. extranea, respectively) and replicate almost exclusively in the midgut epithelial cells (12,29), members of the genus Densovirus have usually a wide host spectrum and, more important, replicate in most larval tissues, with the exception of midgut (2,3,28). As recently clearly demonstrated for vertebrate parvoviruses, these differences might reflect specific requirements for cellular proteins functionning in parternship with NS and (or) VP proteins in order to achieve the viral replicative cycle, as has been recently demonstrated for vertebrate parvoviruses (6,7,22,23,24,30,31).…”

Section: Discussionmentioning

confidence: 91%

NS-3 Protein of the Junonia coenia Densovirus Is Essential for Viral DNA Replication in an Ld 652 Cell Line and Spodoptera littoralis Larvae

Abd-Alla¹,

Jousset²,

Li³

et al. 2004

J Virol

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Finally, we present evidence that NS-1 and NS-2 proteins are synthesized at apparently the same levels whether or not NS-3 is expressed.Densoviruses (DNVs) are autonomously replicating parvoviruses known to be highly pathogenic for two phyla of invertebrates: insects and crustacea (3, 13). Like their vertebrate counterparts, DNVs are small icosahedral nonenveloped viruses with a single-stranded linear DNA genome 4 to 6 kb in length (3,4,26). Based on the size, organization of coding sequences, and structure of extremities of their genome, DNVs are distributed in three genera within the subfamily Densovirinae (5). Members of the genus Densovirus, with the Junonia coenia DNV (JcDNV) as the prototype, have a 6-kb genome, a long (Ͼ500-nucleotide [nt]) inverted terminal repeat (ITR), and an ambisense organization. The four structural proteins VP1, VP2, VP3, and VP4 are nested in a single large open reading frame (ORF), ORF1, located in the 5Ј half of one strand, whereas in the 5Ј half of the complementary strand ORF2, ORF3, and ORF4 encode the three nonstructural (NS) proteins NS-1, NS-2, and NS-3, respectively (11). VP and NS genes are transcribed from the P9 and P93 promoters, respectively. The four overlapping capsid polypeptides are synthesized from an unspliced 2.5-kb mRNA by a "leaky-scanning" mechanism whereby ribosomes initiate translation at the first, second, third, or fourth/fifth in-frame AUG codon. Thus, the four VPs share the same C-terminal sequence and differ only in their N-terminal region. The frequency of translation initiation events at each AUG codon is very likely responsible for the different levels of expression of the four polypeptides, as reflected by the presence of VP1, VP2, VP3, and VP4 in an approximate 1:9:9:41 ratio in the virion (27). The three NS proteins are synthesized from two mRNAs, an unspliced 2.4-kb mRNA coding for NS-3 and a spliced 1.7-kb mRNA coding for NS-1 and NS-2 (unpublished data). Among other functions, these proteins are likely to be involved in viral DNA replication. Sequence analyses revealed that NS-1 proteins of DNVs share homologies with NS-1 proteins of vertebrate parvoviruses, including NTP-binding and helicase activity domains (1,3,11,26). Recent in vitro studies of JcDNV NS-1 biochemical properties have confirmed its involvement in viral DNA replication by showing that it binds to specific DNA sequences within the A-AЈ region of the terminal palindrome and, like its vertebrate counterparts, has multiple functions (including a strand-and site-specific nicking activity), and has an ATPdependent DNA helicase activity (10). In contrast, no clear function could be assigned so far to NS-2 and NS-3 proteins of DNVs. These proteins share no homology with NS proteins of vertebrate parvoviruses or with protein sequences from data banks. In the present study we attempted to elucidate the function of NS-3 in the life cycle of JcDNV by generating deletion mutants and analyzing their ability to undergo a replicative cycle. Our results demonstrate that NS-3 is absolutely

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Section: Discussionmentioning

confidence: 91%

NS-3 Protein of the Junonia coenia Densovirus Is Essential for Viral DNA Replication in an Ld 652 Cell Line and Spodoptera littoralis Larvae

Abd-Alla¹,

Jousset²,

Li³

et al. 2004

J Virol

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“…Once the appropriate cellular conditions are met, the virus starts its replication at the G1/S transition, and a lytic or even productive infection can ensue. Completion of the viral life cycle requires the assistance of various cellular molecules (Raab et al, 2002); some of these have been identified, however, much is unknown. In our study, all samples of FTC were B19 negative by IHC, whereas they showed comparable rates of positivity by PCR and ISH, which indicated that the virus can infect thyroid epithelial cell but was active only in PTC lesions.…”

Section: Discussionmentioning

confidence: 99%

Detection of human parvovirus B19 in papillary thyroid carcinoma

et al. 2008

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To evaluate whether parvovirus B19, a common human pathogen, was also involved in papillary thyroid carcinoma (PTC), 112 paraffin-embedded thyroid specimens of benign nodules, papillary, medullary and follicular carcinomas, and normal controls were examined for B19 DNA and capsid protein by nested PCR, in situ hybridisation (ISH) and immunohistochemistry (IHC). The expression of the nuclear factor-kB (NF-kB) was investigated by IHC. The results showed B19 DNA commonly exists in human thyroid tissues; however, there were significant differences between PTC group and normal controls, and between PTC and nonneoplastic adjacent tissues (Po0.001). The presence of viral DNA in PTC neoplastic epithelium was confirmed by laser-capture microdissection and sequencing of nested PCR products. B19 capsid protein in PTC group was significantly higher than that of all the control groups and nonneoplastic adjacent tissues (Pp0.001). Compared with control groups, the activation of NF-kB in PTC group was significantly increased (Pp0.02), except for medullary carcinomas, and the activation of NF-kB was correlated with the viral protein presence (P ¼ 0.002). Moreover, NF-kB was colocalised with B19 DNA in the neoplastic epithelium of PTC by double staining of IHC and ISH. These results indicate for the first time a possible role of B19 in pathogenesis of PTC.

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“…These findings immediately suggest a mechanism for caspase-dependent ADV replication. Parvoviral NS1 performs several obligatory roles in virus replication that require NS1 translocation into the nucleus (28,38). Since caspase cleavage appeared to be necessary for ADV NS1 to locate in the nucleus, permissive replication can proceed only if caspase cleavage occurs.…”

Section: Discussionmentioning

confidence: 99%

Caspase Cleavage of the Nonstructural Protein NS1 Mediates Replication of Aleutian Mink Disease Parvovirus

Best¹,

Shelton²,

Pompey³

et al. 2003

J Virol

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Virus-induced apoptosis of infected cells can limit both the time and the cellular machinery available for virus replication. Hence, many viruses have evolved strategies to specifically inhibit apoptosis. However, Aleutian mink disease parvovirus (ADV) is the first example of a DNA virus that not only induces apoptosis but also utilizes caspase activity to facilitate virus replication. To determine the function of caspase activity during ADV replication, virus-infected cell lysates or purified ADV proteins were incubated with various purified caspases. Caspases cleaved the major nonstructural protein of ADV (NS1) at two caspase recognition sequences, whereas ADV structural proteins could not be cleaved. Importantly, the NS1 products could be identified in ADV-infected cells but were not present in infected cells pretreated with caspase inhibitors. By mutating putative caspase cleavage sites (D to E), we mapped the two cleavage sites to amino acid residues NS1:227 (INTD2S) and NS1:285 (DQTD2S). Replication of ADV containing either of these mutations was reduced 10 3 -to 10 4 -fold compared to that of wild-type virus, and a construct containing both mutations was replication defective. Immunofluorescent studies revealed that cleavage was required for nuclear localization of NS1. The requirement for caspase activity during permissive replication suggests that limitation of caspase activation and apoptosis in vivo may be a novel approach to restricting virus replication.

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NS1 Protein of Parvovirus B19 Interacts Directly with DNA Sequences of the p6 Promoter and with the Cellular Transcription Factors Sp1/Sp3

Cited by 83 publications

References 35 publications

NS-3 Protein of the Junonia coenia Densovirus Is Essential for Viral DNA Replication in an Ld 652 Cell Line and Spodoptera littoralis Larvae

NS-3 Protein of the Junonia coenia Densovirus Is Essential for Viral DNA Replication in an Ld 652 Cell Line and Spodoptera littoralis Larvae

Detection of human parvovirus B19 in papillary thyroid carcinoma

Caspase Cleavage of the Nonstructural Protein NS1 Mediates Replication of Aleutian Mink Disease Parvovirus

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