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Order Nidovirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The nidoviral genome is an infectious, linear, positive-sense single-stranded RNA molecule, which is capped and polyadenylated. As reviewed by de Groot et al. (2012), the two groups—large and small nidoviruses—can be distinguished by the genome size. The genomes of the large nidoviruses are well over 25 kb in length with size differences in the 5 kb range: 26.4–31.7 kb (Coronavirus), 28–28.5 kb (Torovirus), about 26.6 (Bafinivirus), and 26.2–26.6 kb (Okavirus). The small nidoviruses include the single Arteriviridae family with genomes of 12.7–15.7 kb in length. Therefore, the coronavirus genomes have the longest RNA virus genome known to date. Their RNA-dependent RNA polymerase is also the only one known to display a proofreading function, possibly to stabilize this long RNA sequence. Figure 26.2 presents the general structure of the SARS-CoV-2 genome, which is the most topical kind of nidovirus just now. The 5’-most two-thirds of the genome comprise the two large, partially overlapping ORFs 1a and 1b, which constitute the replicase gene and together encode a collection of enzymes that are part of the replication complex. The virion RNA functions as mRNA1 for the ORFs 1a and 1b, but the expression of the latter requires a programmed ribosomal frameshift.
Translation
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Spanjaard and van Duin (1988) found that the translation of the sequence AGG-AGG yielded 50% ribosomal frameshift. Thus, when the sequence 5′-AAG-GAG-GU-3′, which was complementary to the 3′-terminus of E. coli 16S rRNA, was inserted in a reading frame into the fused MS2 coat-interferon gene (for details, see Chapter 19), just before the interferon part, the translation over the sequence yielded a 50% ribosomal frameshift, if the reading phase was A-AGG-AGG-U. The other two possible frames did not give shifts. The introduction of a UAA stop codon before (UAA-AGG-AGG-U) but not after (A-AGG-AGG-UAA) the AGG codons abolished the frameshift. The change in the reading phase occurred exclusively to the +1 direction. The efficient frameshifting was induced also by the sequence A-AGA-AGA-U. The arginine codons AGG and AGA were read by a minor tRNA and suppression of frameshifting took place when a gene for the minor tRNAArg was introduced on a multicopy plasmid. It was suggested that frameshifting during translation of the A-AGG-AGG-U sequence was due to the erroneous decoding of the tandem AGG codons and arose by depletion of the tRNAArg. Therefore, the complementarity of tandem AGG codons to the 3′-terminus of 16S rRNA was regarded as a coincidence and apparently not related to the shift. However, replacing the AGG-AGG sequence by the optimal arginine codons CGU-CGU did not increase the overall rate of translation (Spanjaard and van Duin 1988).
Introduction to virus structure, classification, replication, and hosts
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Philippe Simon, Kevin M. Coombs
The viral genome may range in size and configuration. The term genome refers to all the nucleic acid of a virus, whereas gene usually refers to the part of the nucleic acid genome that encodes a specific viral protein. The smallest viruses (e.g., parvoviruses) have genomes of approximately 5000 nucleotides (=5 kilobases, or 5 kb) that contain two genes. The largest human viruses (e.g., poxviruses and herpesviruses) can have genomes larger than 200 kilobase pairs (200 kbp; “pairs” because their nucleic acid is double-stranded) and can therefore potentially encode more than 250 proteins. Pandoraviruses, a member of the amoeba-infecting “giant virus” group, have a genome of approximately 1.9–2.5 million bp which could potentially encode over 2500 proteins [4]. Most viruses have genomes whose sizes fall between these extremes. For most families of viruses, all viral genes are located on a single contiguous linear piece of nucleic acid, with the same gene generally located in the same position on the genome in every virion within that family. A few viruses (e.g., hepatitis B virus, a member of the Hepadnaviridae, which, because it is not known to be neurotropic, is not covered in this volume and the Polyomaviridae, which includes the neurotropic JC virus) have a circular rather than linear genome. Some viruses have segmented genomes. For example, the human influenza virus genome consists of eight separate segments of RNA that encode at least 15 different proteins. To optimize genome size, five of the eight RNA segments encode more than one protein due to alternative splicing or initiation or ribosomal frameshift. To be infectious, a virion must contain at least one copy of each of the eight gene segments, although recent research has highlighted the possibility that influenza viruses may behave similarly to multipartite viruses [5]. Likewise, the Reoviridae genome consists of 9–12 segments (depending upon the specific genus of virus) of double-stranded RNA, all of which must be present in a virion for it to be infectious. The segmented nature of these types of viral genomes has dramatic ramifications with regard to their pathogenesis (reviewed in Refs. [6,7]).
Enteroviruses and coronaviruses: similarities and therapeutic targets
Published in Expert Opinion on Therapeutic Targets, 2021
Varpu Marjomäki, Kerttu Kalander, Maarit Hellman, Perttu Permi
The coronaviruses have a polycistronic genome organization [28]. The structural proteins are encoded in the 3´end of the genome and expressed from a nested set of subgenomic mRNAs after a discontinuous transcription. The replicase proteins are encoded by two 5´end open reading frames 1a and 1b (ORF1a and ORF1b), connected by a ribosomal frameshift site. The translation products of ORF1a and ORF1b are cleaved by viral proteases at 14 sites. The envelope-located spike protein will undergo co-translational processing of the glycoprotein and maturation cleavages along the exocytic pathway on its way to the plasma membrane. The varying activities and kinetics of the viral proteases to release the replicase components and accessory proteins have a strong regulatory effect on the replication and pose a valid target for antiviral action. The synthesis of both negative and positive RNA occurs in double membrane vesicles [37]. The positive strand RNA copies are transferred through a pore through the double membrane vesicles, after which N proteins start encapsidation of the genomic RNA to the assembling virions [38].
Coronavirus helicases: attractive and unique targets of antiviral drug-development and therapeutic patents
Published in Expert Opinion on Therapeutic Patents, 2021
Austin N. Spratt, Fabio Gallazzi, Thomas P. Quinn, Christian L. Lorson, Anders Sönnerborg, Kamal Singh
CoVs are large (15–30 kb) positive (+) single-stranded RNA viruses. The polyadenylated and capped RNA genome has open reading frames (ORFs) that encode pp1a and pp1ab through a − 1 ribosomal frameshift during translation [16,17]. These large polyproteins are proteolytically cleaved to generate mature CoV non-structural proteins (nsp) as well as the structural and accessory proteins [10,18–24]. The polyproteins are processed by a virus-encoded papain-like proteinases (PLpro; within nsp3) [25] and nsp5 (3 CLpro) [10,16,19,26–29] to yield up to 16 nsps with diverse functions and up to 10 structural proteins that facilitate viral assembly [30–34]. The singular helicase protein of hCoVs is encoded by nsp13 [12]. nsp13, in concert with additional nsp proteins, assembles into a replication-transcription complex that binds to the 3ʹ untranslated region of the genomic RNA and generates (-) strand RNA as well as subgenomic RNAs [30–34]. A recent review has covered patented inhibitors of different CoV targets [35], here we have focused on the patented inhibitors of nsp13.
Research progress in the development of porcine reproductive and respiratory syndrome virus as a viral vector for foreign gene expression and delivery
Published in Expert Review of Vaccines, 2020
Guo Dai, Mei Huang, To Sing Fung, Ding Xiang Liu
As illustrated in Figure 1, PRRSV is a single-stranded, positive-sense (+) enveloped RNA virus with a genome of about 15 kb. The RNA genome includes the cap structure and the untranslated region (UTR) at the 5ʹ-end, UTR and poly (A) tail at the 3ʹ-end. It encodes at least 10 open reading frames (ORFs) between the 5ʹ- and the 3ʹ-ends, designated ORF1a, ORF1b, ORF2a, ORF2b, ORF3–7 and ORF5a [8–10]. ORF1a and ORF1b, account for three-quarters of the viral genome, mainly encode large replicase polyproteins pp1a, pp1a-nsp2N, pp1a-nsp2TF, and pp1ab via ribosomal frameshift (RFS). These polyproteins are proteolytically processed into nearly 16 functional nonstructural proteins (nsps), including nsp1α, nsp1β, nsp2TF, nsp2N, nsp2–6, nsp7α, nsp7β and nsp8–12, functionally responsible for the viral genome replication and transcription [5,11].