We have determined the nucleotide sequence of sacbrood virus (SBV), which causes a fatal infection of honey bee larvae. The genomic RNA of SBV is longer than that of typical mammalian picornaviruses (8832 nucleotides) and contains a single, large open reading frame (179-87521 encoding a polyprotein of 2858 amino acids. Sequence comparison with other virus polyproteins revealed regions of similarity to characterized helicase, protease and RNA-dependent RNA polymerase domainsl structural genes were located at the 5' terminus with non-structural genes at the 3' end. Picornavirus-like agents of insects have two distinct genomic organizations; some resemble mammalian picornaviruses with structural genes at the 5' end and non-structural genes at the 3' end, and others resemble caliciviruses in which this order is reversed I SBV thus belongs to the former type. Sequence comparison suggested that SBV is distantly related to infectious flacherie virus (lFV) of the silk worm, which possesses an RNA of similar size and gene order.

We have determined the complete genomic sequence of human astrovirus serotype 1 isolated in Newcastle upon Tyne. The genome is 6813 nucleotides long and contains three sequential open reading frames (ORFs). The two closest to the 5' end are linked by a ribosomal frameshifting motif and contain sequence motifs indicative of non-structural virus proteins: serine protease and RNA-dependent RNA polymerase. A nuclear addressing sequence is also located here. The 3' ORF encodes the virion structural polypeptides as a polyprotein precursor. This genomic organization resembles that of the plant virus family Luteoviridae.

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The RNA genome of Seneca Valley virus (SVV), a recently identified picornavirus, contains an internal ribosome entry site (IRES) element which has structural and functional similarity to that from classical swine fever virus (CSFV) and hepatitis C virus, members of the Flaviviridae. The SVV IRES has an absolute requirement for the presence of a short region of virus-coding sequence to allow it to function either in cells or in rabbit reticulocyte lysate. The IRES activity does not require the translation initiation factor eIF4A or intact eIF4G. The predicted secondary structure indicates that the SVV IRES is more closely related to the CSFV IRES, including the presence of a bipartite IIId domain. Mutagenesis of the SVV IRES, coupled to functional assays, support the core elements of the IRES structure model, but surprisingly, deletion of the conserved IIId 2 domain had no effect on IRES activity, including 40S and eIF3 binding. This is the first example of a picornavirus IRES that is most closely related to the CSFV IRES and suggests the possibility of multiple, independent recombination events between the genomes of the Picornaviridae and Flaviviridae to give rise to similar IRES elements.Seneca Valley virus (SVV) is a recently discovered member of the picornavirus family. It was found as a contaminant in PER.C6 cell cultures, and its natural host has not yet been definitively identified, but a number of closely related viruses have been isolated from pigs (16). The complete genome sequence of SVV-001 (16) and the crystal structure of the virus capsid (52) have now been determined. The virus is most closely related to the cardioviruses, but there are some significant differences (see below), and hence it has been recommended that the virus is classified as a new species within a new genus (Senecavirus) of the Picornaviridae.SVV-001 and two of the related viruses (isolates 1278 and 66289) were inoculated into pigs; evidence of viral replication was obtained for all three viruses and for transmission of isolate 66289. However, in none of the experiments was any sign of illness observed (unpublished data and personal communication from J. Landgraf, USDA). An important feature of SVV is its ability to replicate selectively within human tumor cells. Owing to this novel activity and lack of observed pathogenicity in animals and humans, there is interest in using SVV as an oncolytic virus against neuroendocrine cancers (39), for which it is currently in clinical trials.All picornaviruses have a positive-sense, single-stranded RNA genome that is infectious and has to act both as an mRNA and as a template for RNA replication (32). Picornavirus RNA includes a single large open reading frame (ORF), encoding a polyprotein, which is flanked by a long 5Ј untranslated region (UTR) of approximately 600 to 1,300 nucleotides (nt) (depending on the virus) plus a shorter 3Ј UTR (Ͻ100 nt) with a poly(A) tail. The viral RNA lacks the 5Ј m 7 GpppN... cap structure found on all eukaryotic cytoplasmic mRNAs. Instead, a small virus-enco...

Viral infections impose major stress on the host cell. In response, stress pathways can rapidly deploy defence mechanisms by shutting off the protein synthesis machinery and triggering the accumulation of mRNAs into stress granules to limit the use of energy and nutrients. Because this threatens viral gene expression, viruses need to evade these pathways to propagate. Human norovirus is responsible for gastroenteritis outbreaks worldwide. Here we examined how norovirus interacts with the eIF2α signaling axis controlling translation and stress granules. While norovirus infection represses host cell translation, our mechanistic analyses revealed that eIF2α signaling mediated by the stress kinase GCN2 is uncoupled from translational stalling. Moreover, infection results in a redistribution of the RNA-binding protein G3BP1 to replication complexes and remodelling of its interacting partners, allowing the avoidance from canonical stress granules. These results define novel strategies by which norovirus undergo efficient replication whilst avoiding the host stress response and manipulating the G3BP1 interactome.