The complete sequence of a human astrovirus

Willcocks, M. M.; Brown, T. D. K.; Madeley, C. R.; Carter, M. J.

doi:10.1099/0022-1317-75-7-1785

Cited by 118 publications

(101 citation statements)

References 23 publications

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“…It was, therefore, of great help that we initially obtained two sequences located about 2 kb apart, facilitating the rapid amplification and sequence determination of the 39 two-thirds of the genome. The presence of poly(A) tails in all 39 most sequence parts indicated that the genome is polyadenylated, as is the case for all other astroviruses for which full-length sequences have been determined to date (Imada et al, 2000;Jiang et al, 1993;Koci et al, 2000;Lewis et al, 1994;Mendez-Toss et al, 2000;Oh & Schreier, 2001;Willcocks et al, 1994). The 59 most extreme sequence proved to be more difficult to obtain.…”

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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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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“…In addition to humans, members of this virus family infect a variety of other young mammals and birds, causing diseases ranging from diarrhea to nephritis (18). Astroviruses are small, nonenveloped, icosahedral particles with a single-stranded mRNA genome (ϳ7 kb) that is organized into three open reading frames (ORFs); ORFs 1a and 1b encode nonstructural proteins (11,16,34), whereas ORF2 encodes the coat protein (CP) precursor (16,32). CP precursors assemble into particles, encapsidating the viral genome, and are subsequently cleaved extracellularly by trypsin, which renders the virion infectious (1,20).…”

mentioning

confidence: 99%

Human Astrovirus Coat Protein Inhibits Serum Complement Activation via C1, the First Component of the Classical Pathway

Bonaparte¹,

Hair

Banthia³

et al. 2008

J Virol

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Human astroviruses (HAstVs) belong to a family of nonenveloped, icosahedral RNA viruses that cause noninflammatory gastroenteritis, predominantly in infants. Eight HAstV serotypes have been identified, with a worldwide distribution. While the HAstVs represent a significant public health concern, very little is known about the pathogenesis of and host immune response to these viruses. Here we demonstrate that HAstV type 1 (HAstV-1) virions, specifically the viral coat protein (CP), suppress the complement system, a fundamental component of the innate immune response in vertebrates. HAstV-1 virions and purified CP both suppress hemolytic complement activity. Hemolytic assays utilizing sera depleted of individual complement factors as well as adding back purified factors demonstrated that HAstV CP suppresses classical pathway activation at the first component, C1. HAstV-1 CP bound the A chain of C1q and inhibited serum complement activation, resulting in decreased C4b, iC3b, and terminal C5b-9 formation. Inhibition of complement activation was also demonstrated for HAstV serotypes 2 to 4, suggesting that this phenomenon is a general feature of these human pathogens. Since complement is a major contributor to the initiation and amplification of inflammation, the observed CP-mediated inhibition of complement activity may contribute to the lack of inflammation associated with astrovirus-induced gastroenteritis. Although diverse mechanisms of inhibition of complement activation have been described for many enveloped animal viruses, this is the first report of a nonenveloped icosahedral virus CP inhibiting classical pathway activation at C1.

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“…[89][90][91][92] Human AstVs are among the leading causative agents of viral gastroenteritis in young children. 93 Although AstV particles have been found in intestinal epithelial cells of children with diarrhea, indicating shedding through feces, the pathology and immunity to AstV infection remains unclear.…”

Section: Astrovirusmentioning

confidence: 99%

Viral-derived complement inhibitors: current status and potential role in immunomodulation

Zaraket

2016

Exp Biol Med (Maywood)

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The complement system is one of the body's major innate immune defense mechanisms in vertebrates. Its function is to detect foreign bodies and promote their elimination through opsonisation or lysis. Complement proteins play an important role in the immunopathogenesis of several disorders. However, excessive complement activation does not confer more protection but instead leads to several autoimmune and inflammatory diseases. With inappropriate activation of the complement system, activated complement proteins and glycoproteins may damage both healthy and diseased tissues. Development of complement inhibitors represents an effective approach in controlling dysregulated complement activity and reducing disease severity, yet few studies have investigated the nature and role of novel complement inhibitory proteins of viral origin. Viral complement inhibitors have important implications in understanding the importance of complement inhibition and their role as a promising novel therapeutic approach in diseases caused by dysregulated complement function. In this review, we discuss the role and importance of complement inhibitors derived from several viruses in the scope of human inflammatory and autoimmune diseases.

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The complete sequence of a human astrovirus

Cited by 118 publications

References 23 publications

Molecular characterization of a novel astrovirus associated with disease in mink

Molecular characterization of a novel astrovirus associated with disease in mink

Human Astrovirus Coat Protein Inhibits Serum Complement Activation via C1, the First Component of the Classical Pathway

Viral-derived complement inhibitors: current status and potential role in immunomodulation

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