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Order Sobelivirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Figure 28.2 shows the genomic structure of the two families of the Sobelivirales order. The genome of the Solemoviridae family comprises a polycistronic, positive-sense, single-stranded RNA molecule of 4–4.6 kb. The genome organization is conserved, with 4–5 ORFs. The protein VPg is covalently attached to the 5′-terminus of viral and subviral RNAs, interacts with the translation initiation complex, and regulates the activity of viral protease and viral RNA-directed RNA polymerase (RdRP), expressed by means of ribosomal frameshifting. The two variants of the polyprotein are translated via a ribosomal leaky scanning mechanism from genomic RNA, and they undergo proteolytic processing at conserved cleavage sites between the domains. The coat protein (CP) is translated from the subgenomic RNA. The 3′-terminus is nonpolyadenylated but has a stable stem-loop or tRNA-like structure (Sõmera et al. 2021).
Introduction to virus structure, classification, replication, and hosts
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Philippe Simon, Kevin M. Coombs
Viral proteins can be generally classified as either structural or nonstructural. By convention, structural proteins are those that are present within a virion particle. Their identities are usually determined by examining the protein content of highly purified preparations of viral particles. For any given virus there is usually a fixed and characteristic number of proteins located within the virion. For example, poliovirus virions contain a single copy of one protein (called VPg) (VP usually indicates virion protein) and 60 copies each of four other proteins (called VP1, VP2, VP3, and VP4). By contrast, nonstructural proteins are those that are encoded by the virus and are found in infected cells but not within the purified virion. Nonstructural proteins are generally enzymatic. They carry out specific enzymatic functions within the cell but are not included within the viral particle. However, some structural proteins also may be enzymes. Within the virion the viral nucleic acid, whether RNA or DNA, is usually surrounded by a protective protein coat built from structural proteins. Because the genetic code is such that nucleotide base triplets encode each amino acid, it is not possible for any genetic material to encode a single protein sufficiently large to protect the genome that encodes it. Thus, for genetic efficiency the protective protein coat is usually constructed from multiple copies of one or a few proteins.
Enterovirus
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Enterovirus multiplies primarily in the gastrointestinal tract and the upper respiratory tract or sometimes both, but occasionally in nerve, muscle, and other tissues [12]. After taking up via the fecal-oral or respiratory route, enterovirus attaches to a cellular receptor (e.g., CD155 or poliovirus receptor/PVR in poliovirus, integrin VLA-2 in echovirus 1, sialic acid in enterovirus D70, and intercellular adhesion molecule 1/ICAM-l in rhinovirus) on the cell surface. This causes an irreversible conformational change in the virion, which leads to the release of VP4 that opens a pore in the host endosomal membrane, through which the viral genomic RNA enters into the host cell cytoplasm. After internalization, viral replication in complexes associated with cytoplasmic membranes begins with the removal of Vpg from the positive-stranded viral RNA, which functions as mRNA for immediate translation into a polyprotein by the host cell (as the virus has the ability to inhibit host cellular protein synthesis in favor of virus-specific protein production). The polyprotein is then autocleaved by internal proteases into 11 individual viral proteins. The availability of new viral proteins facilitates synthesis of the dsRNA genome from the genomic ssRNA(+), transcription amd replication of dsRNA genome into ssRNA(+) genomes. The newly assembled enterovirus leaves after lysis of the host cell, usually 4–6 hours following the initiation of infection, and is shed in respiratory secretions and stool and sometimes the blood and cerebrospinal fluid.
Human rhinovirus infection and COPD: role in exacerbations and potential for therapeutic targets
Published in Expert Review of Respiratory Medicine, 2020
John Cafferkey, James Andrew Coultas, Patrick Mallia
The other regions of the virus genome encode the aforementioned proteases, a polymerase for RNA replication and proteins required for virus invasion of host cells [75]. The P2 region codes for 3 proteins: protein 2A is a cysteine protease that targets the P1-P2 junction and cleaves the initial viral polyprotein into its constituent proteins [74], protein 2B acts as a viroporin whilst protein 2C binds various intracellular structures. In the P3 region, protein 3A facilitates virus replication through the PI4KB protein which has become a target for potential antiviral therapies [77]. 3B has a less clear role but appears to assist with viral replication [78]. 3 C is a protease that plays immunomodulatory roles by cleaving retinoic acid-inducible gene I (RIG-I) leading to reduced type I interferon production [79]. 3Dpol is a RNA-dependent RNA polymerase (RdRps) that synthesizes viral RNA during replication. The polymerase utilizes VPg (small viral peptide) as a primer in this process [80].
The potential of plant-made vaccines to fight picornavirus
Published in Expert Review of Vaccines, 2020
Omayra C. Bolaños-Martínez, Sergio Rosales-Mendoza
Picornaviridae is one of the largest viral families, which according to the International Committee on Taxonomy of Viruses (ICTV) comprise 35 genera enclosing 80 viral species; many other are on the list to be classified. All members are ~30-32 nm in diameter with an icosahedral structure composed of 60 identical units (protomers) [1]. The members of this family have a genome composed of a single-stranded, positive-sense, and non-segmented RNA; with a length ranging 6.7–10.1 kb. The ORF is flanked by two untranslated regions (UTR); with the 5´end containing diverse RNA secondary structures implicated in replication and associated with the VPg protein that plays an important role in translation. The 3´UTR contains a poly (A) tail that mimics mRNA from the host providing genome stability (Figure 1). Picornaviruses possess four capsid proteins having b-barrel folding and code for a polyprotein that is processed by virus-encoded cysteine proteinases; their replication is performed by an RNA-dependent RNA polymerase containing the YGDD sequence motif. Picornaviruses are transmitted through the oral-fecal or aerial routes and many of them affect humans and animals; causing subclinical infections, mild febrile illness, and mild diseases in the gastrointestinal or respiratory tracts; as well as severe heart, liver, and central nervous system diseases. Picornaviruses of the genera Cardiovirus, Cosavirus, Enterovirus, Hepatovirus, Kobuvirus, Parechovirus, and Salivirus infect humans [2].
Enteroviruses and coronaviruses: similarities and therapeutic targets
Published in Expert Opinion on Therapeutic Targets, 2021
Varpu Marjomäki, Kerttu Kalander, Maarit Hellman, Perttu Permi
Enteroviruses are known to trigger their RNA synthesis by covalently modifying one of their non-structural proteins, the VPg (Viral protein genome-linked) protein [61]. First, VPg is cleaved from the large polyprotein by the viral protease precursor 3 CD. Then, viral 3D polymerase will covalently link the VPg peptide with uridine monophosphate resulting in a VPg-pU. This peptide is then linked with another monophosphate to create a dinucleotide that will then bind to the viral poly(A)template to start the viral synthesis [62]. VPg will remain covalently attached to the forming genomic RNA. Now, very recently, it was discovered that an analogous transfer of a nucleoside monophosphate to a nonstructural protein 9 is essential for coronaviruses replication [40] The non-structural protein 9 is an RNA-binding protein and known to be involved in coronavirus replication [63]. It was discovered that a Nidovirus-specific RdRp-associated Nucleotidyl transferase domain (NiRAN) in a nonstructural protein 12 has catalytic activity to transfer a nucleoside monophosphate to the amino terminus of the non-structural protein 9 [40]. This transfer preferentially uses uridine nucleotides, although the NiRAN domain is also ableto catalyze other nucleotides [40]. Before the transfer, similar to enteroviruses, the main protease releases both the nonstructural proteins 12 and 9 from the polyprotein. In addition to Nsp9, similar catalytic activity of NiRAN in the non-structural protein 12 was suggested to also involve the non-structural protein 8 (Nsp8; 41). In this recent article by Shannon and coworkers (2021), Nsp12 was shown to uridylate a viral cofactor of non-structural protein 8, thus forming a UMP-Nsp8 covalent intermediate that can prime RNA synthesis from a poly(A) template. Importantly, a 5´-triphosphate analogue, AT-9010 was shown to bind tightly to NiRAN and inhibit uridylylation of Nsp8 and RNA synthesis. AT-9010 is presently in phase II clinical trials and thus is a promising antiviral candidate for coronaviruses. It will be interesting to find out in future studies, whether the functions of the primed nonstructural proteins 8 and 9 are similar, and if the priming of the non-structural protein 9 can be also halted with AT-9010.