An astrovirus frameshift signal induces ribosomal frameshifting in vitro

Lewis, Terry L.; Matsui, Shigeru

doi:10.1007/bf01315421

Cited by 40 publications

(37 citation statements)

References 32 publications

(49 reference statements)

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“…The 76-kDa band may be explained by the occurrence of a frameshift after aa 903 of nsP1a that led to the translation of the 122 ORF1b-derived amino acids followed by 11 vector-encoded amino acids (expected molecular mass of the fusion protein, 72 kDa). The prominence of the 76-kDa band suggests that during translation of His-394-nsP1a, frameshifting occurs at a frequency higher than the 5 to 7% reported previously (13). This may be due to an altered conformation of the nascent His-394-nsP1a during translation compared to that of the full-length nsP1a.…”

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confidence: 43%

“…The translation product of ORF1a is designated nonstructural protein 1a (nsP1a). Expression of ORF1b, which is in a Ϫ1 position relative to ORF1a, depends on the occurrence of a Ϫ1 ribosomal frameshift during the translation of ORF1a (5 to 7% frequency in a cell-free, uncoupled transcription-translation system [13]), leading to an nsP1a/1b fusion protein (13,14). ORF2 encodes the viral capsid protein and is expressed from a subgenomic RNA colinear with the 3Ј one-third of the genomic RNA (12,17).…”

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confidence: 99%

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Processing of Nonstructural Protein 1a of Human Astrovirus

Geigenmüller

Chew

Ginzton

et al. 2002

J Virol

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Astrovirus contains three open reading frames (ORF) on its genomic RNA, ORF1a, ORF1b, and ORF2. ORF1a encodes a 920-amino-acid (aa) nonstructural protein, nsP1a, which displays a 3C-like serine protease motif. Little is known about the processing of nsP1a or whether the protease it contains is active and involved in autocatalytic processing. Here we address both of these matters. Intact and N-terminally deleted forms of ORF1a from human astrovirus serotype 1 were expressed in BHK cells, and nsP1a-derived processing products were immunoprecipitated with an nsP1a-specific antibody or an antibody specific for an N-terminally linked epitope tag. The mapping of the main processing products, p20 and p27, suggests cleavage sites near aa 170, 410, and 655 of nsP1a. Cleavages at around aa 410 and 655, but not aa 170, were abolished when a 9-aa substitution was introduced into the protease motif in nsP1a. The p27 processing product was also found in Caco-2 cells that had been infected with human astrovirus serotype 1, confirming the presence of the cleavage sites at approximately aa 410 and 655.

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confidence: 43%

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confidence: 99%

Processing of Nonstructural Protein 1a of Human Astrovirus

Geigenmüller

Chew

Ginzton

et al. 2002

J Virol

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“…The ribosomal frameshift sequence linking ORF1a and 1b is a feature typical of astroviruses (Lewis & Matsui, 1995, 1996, 1997Marczinke et al, 1994), as are the amino acid motifs for a serine protease in ORF1a and the RdRp of the picornavirus supergroup lacking a helicase motif in ORF1b. Comparisons of the deduced amino acid sequences from ORF1a, 1b and 2 of MiAstV with the corresponding ORFs of its closest relative, OAstV, revealed identities of 38, 63 and 37 %, respectively.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of a novel astrovirus associated with disease in mink

Mittelholzer

Hedlund

Englund

et al. 2003

Journal of General Virology

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Pre-weaning diarrhoea is a well-known problem in mink farming in Europe, causing morbidity that varies between farms, regions and season. Different causalities for the disease have been proposed, but only most recently has a novel astrovirus been identified as an important risk factor. In this report, the molecular characterization, origin and evolution of this novel astrovirus of mink are discussed. The polyadenylated, positive-stranded RNA genome was sequenced and found to contain 6610 nt, organized into three ORFs and two short UTRs. A ribosomal frameshift sequence links the 59 two ORFs, containing sequence motifs for a serine protease (ORF1a) and an RNA-dependent RNA polymerase (ORF1b). The structural proteins are encoded by ORF2 and, presumably, are expressed as a polyprotein precursor to be cleaved into the mature capsid proteins. These results indicate that mink astrovirus (MiAstV) has all of the features typical of members of the Astroviridae. Phylogenetic analyses revealed that MiAstV is distantly related to established astroviruses, showing less than 67 % similarity at the nucleotide level with its closest relative, ovine astrovirus, and even lower identities at the predicted amino acid level. Nevertheless, sequence analysis of MiAstV isolates from geographically distinct Swedish and Danish farms showed much less diversity. This suggests either the spread in the mink population of a virus that has evolved a long time ago or the recent introduction of an ancient virus into a new host species. INTRODUCTIONFor several decades, a pre-weaning diarrhoea syndrome with unknown aetiology has been observed in mink farms in Europe. Numerous investigations studying the causality of this clinical syndrome have been conducted and various agents have been discussed as possible causes, but only recently did a case-controlled study reveal the presence of an astrovirus as a significant risk factor (Englund et al., 2002).Astroviruses were named by Madeley & Cosgrove (1975) after their star-like appearance in electron microscopy; the name astrovirus comes from 'astron', which means star in Greek. Astroviruses are an important cause of acute infantile gastroenteritis in humans (Madeley & Cosgrove, 1975) and have been shown to infect sheep (Snodgrass & Gray, 1977), cattle (Woode & Bridger, 1978), dog (Williams, 1980), domestic cat (Hoshino et al., 1981), red deer (Tzipori et al., 1981), duck (Gough et al., 1984), mouse (Kjeldsberg & Hem, 1985), turkey (McNulty et al., 1980) and pig (Shimizu et al., 1990), causing various syndromes, ranging from mild diarrhoea in lambs (Snodgrass et al., 1979) and poult enteritis and mortality syndrome in turkeys (Yu et al., 2000) to acute nephritis in chickens (Imada et al., 2000).The genome of astroviruses consists of a positive-stranded, polyadenylated RNA, which is about 7 kb long and contains three ORFs, designated ORF1a, ORF1b and ORF2 (Monroe et al., 1995). Whereas the latter encodes the capsid protein(s), ORF1a and 1b encode the nonstructural proteins involved in replication. All ast...

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“…ORF1a encodes a polypeptide of 920 to 935 amino acids (aa) containing several conserved motifs, including a serine protease (11,44). A highly conserved heptanucleotide motif and downstream hairpin structure at the ORF1a-ORF1b junction generates a Ϫ1 frameshift, leading to the translation of an ORF1a-ORF1b polypeptide which is later cleaved into polypeptides corresponding to ORF1a and ORF1b (11,29,41,44). ORF1b encodes a polypeptide of approximately 515 to 528 aa, containing the RNA-dependent RNA polymerase (RdRP) (40,44).…”

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Adaptive Immunity Restricts Replication of Novel Murine Astroviruses

Yokoyama

Loh

Zhao

et al. 2012

J Virol

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The mechanisms of astrovirus pathogenesis are largely unknown, in part due to a lack of a small-animal model of disease. Using shotgun sequencing and a custom analysis pipeline, we identified two novel astroviruses capable of infecting research mice, murine astrovirus (MuAstV) STL1 and STL2. Subsequent analysis revealed the presence of at least two additional viruses (MuAstV STL3 and STL4), suggestive of a diverse population of murine astroviruses in research mice. Complete genomic characterization and subsequent phylogenetic analysis showed that MuAstV STL1 to STL4 are members of the mamastrovirus genus and are likely members of a new mamastrovirus genogroup. Using Rag1 ؊/؊ mice deficient in B and T cells, we demonstrate that adaptive immunity is required to control MuAstV infection. Furthermore, using Stat1 ؊/؊ mice deficient in innate signaling, we demonstrate a role for the innate immune response in the control of MuAstV replication. Our results demonstrate that MuAstV STL permits the study of the mechanisms of astrovirus infection and host-pathogen interactions in a genetically manipulable smallanimal model. Finally, we detected MuAstV in commercially available mice, suggesting that these viruses may be present in academic and commercial research mouse facilities, with possible implications for interpretation of data generated in current mouse models of disease.

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An astrovirus frameshift signal induces ribosomal frameshifting in vitro

Cited by 40 publications

References 32 publications

Processing of Nonstructural Protein 1a of Human Astrovirus

Processing of Nonstructural Protein 1a of Human Astrovirus

Molecular characterization of a novel astrovirus associated with disease in mink

Adaptive Immunity Restricts Replication of Novel Murine Astroviruses

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