Recent Progress in Torovirus Molecular Biology

Ujike, Makoto; Taguchi, Fumihiro

doi:10.3390/v13030435

Cited by 13 publications

(12 citation statements)

References 224 publications

(311 reference statements)

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“…Both structures have similar predicted minimum free energy. The insertion involves the TRS-B sequence located in the intergenic region between ORF8 and N genes and is preceded by a uridine-adenosine (U/A)-rich region including a sequence similar to the torovirus attenuation sequence [ 56 ], which like TRS-B, might cause the RNA-dependent RNA polymerase to pause, thereby facilitating the intragenomic rearrangement as it is theorized to do during subgenomic RNA synthesis. Additional file 1 : Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Stop codon of ORF8 protein is depicted with a red asterisk, and initiation codon of N is in green letters. TRS-B core sequence and complementary TRS-Bs in ORF8 and in ORF8x are highlighted in blue; and the uridine/adenosine tracks, including the torovirus-like attenuation sequence [56] are highlighted in fuchsia. 5′-UTR nucleotide and predicted translated amino acid sequences in ORF8X are in bold letters and highlighted in green intergenic region with a second and closer complementary TRS-B, yielding a similar predicted minimum free energy.…”

Section: Intragenomic Rearrangements At the Distal End Of Orf8 And Or...mentioning

confidence: 99%

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Intragenomic rearrangements involving 5′-untranslated region segments in SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses

Patarca

Haseltine

2023

Virol J

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Background Variation of the betacoronavirus SARS-CoV-2 has been the bane of COVID-19 control. Documented variation includes point mutations, deletions, insertions, and recombination among closely or distantly related coronaviruses. Here, we describe yet another aspect of genome variation by beta- and alphacoronaviruses that was first documented in an infectious isolate of the betacoronavirus SARS-CoV-2, obtained from 3 patients in Hong Kong that had a 5′-untranslated region segment at the end of the ORF6 gene that in its new location translated into an ORF6 protein with a predicted modified carboxyl terminus. While comparing the amino acid sequences of translated ORF8 genes in the GenBank database, we found a subsegment of the same 5′-UTR-derived amino acid sequence modifying the distal end of ORF8 of an isolate from the United States and decided to carry out a systematic search. Methods Using the nucleotide and in the case of SARS-CoV-2 also the translated amino acid sequence in three reading frames of the genomic termini of coronaviruses as query sequences, we searched for 5′-UTR sequences in regions other than the 5′-UTR in SARS-CoV-2 and reference strains of alpha-, beta-, gamma-, and delta-coronaviruses. Results We here report numerous genomic insertions of 5′-untranslated region sequences into coding regions of SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses, but not delta- or gammacoronaviruses. To our knowledge this is the first systematic description of such insertions. In many cases, these insertions would change viral protein sequences and further foster genomic flexibility and viral adaptability through insertion of transcription regulatory sequences in novel positions within the genome. Among human Embecorivus betacoronaviruses, for instance, from 65% to all of the surveyed sequences in publicly available databases contain inserted 5′-UTR sequences. Conclusion The intragenomic rearrangements involving 5′-untranslated region sequences described here, which in several cases affect highly conserved genes with a low propensity for recombination, may underlie the generation of variants homotypic with those of concern or interest and with potentially differing pathogenic profiles. Intragenomic rearrangements thus add to our appreciation of how variants of SARS-CoV-2 and other beta- and alphacoronaviruses may arise.

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Section: Resultsmentioning

confidence: 99%

Section: Intragenomic Rearrangements At the Distal End Of Orf8 And Or...mentioning

confidence: 99%

Intragenomic rearrangements involving 5′-untranslated region segments in SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses

Patarca

Haseltine

2023

Virol J

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“…Stop codon of ORF8 is depicted with a red asterisk, and initiation codon of N is in green letters. TRS-B core sequence and complementary TRS-Bs in ORF8 and in ORF8x are highlighted in blue; and the uridine/adenosine tracks, including the torovirus-like attenuation sequence (Ujike and Taguchi. 2021) are highlighted in fuchsia.…”

Section: Resultsmentioning

confidence: 99%

“…Both structures have similar predicted free minimum energy. The insertion involves the TRS-B sequence located in the intergenic region between ORF8 and N and is preceded by a uridine-adenosine (U/A)-rich region including a sequence similar to that of the torovirus attenuation sequence (Ujike and Taguchi 2021), which like TRS-B, could cause the RNA-dependent RNA polymerase to pause, thereby facilitating the intragenomic rearrangement as it is theorized to do during subgenomic RNA synthesis. Supplemental Figure 1 shows the predicted RNA structures of the most common ORF8x variants with similar predicted minimum free energy, and Supplemental Figure 2 shows an alternative RNA structure involving the interaction between the TRS-B in the intergenic region with a second and closer complementary TRS-B, yielding a similar predicted minimum free energy.…”

Section: Resultsmentioning

confidence: 99%

Intragenomic rearrangements of SARS-CoV-2 and other β-coronaviruses

Patarca

Haseltine

2022

Preprint

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The continuation of the SARS-CoV-2 pandemic depends on the generation of new viral variants. Documented variation includes point mutations, deletions, insertions, and recombination among closely or distantly related coronaviruses. Here, we describe yet another aspect of genome variation by β-coronaviruses, including SARS-CoV-2. Specifically, we report numerous genomic insertions of 5′-untranslated region sequences into coding regions of SARS-CoV-2 and other beta-coronaviruses. To our knowledge this is the first systematic description of such insertions. In many cases, these insertions change viral protein sequences and further foster genomic flexibility and viral adaptability through insertion of transcription regulatory sequences in novel positions within the genome. Among human Embecorivus β-coronaviruses, for instance, from one-third to one-half of surveyed sequences in publicly available databases contain 5′-UTR-derived inserted sequences. In limited instances, there is mounting evidence that these insertions alter the fundamental biological properties of mutant viruses. Intragenomic rearrangements add to our appreciation of how SARS-CoV-2 variants may arise.

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“…Nidovirales can infect both vertebrates ( Coronaviridae, Arteriviridae, and Roniviridae ) and invertebrates ( Mesoniviridae ) ( Table 1 ), with a wide range of host organisms, from mammal to bird, fish, crustacean, and insect ( Cavanagh et al, 1994 ; Snijder and Meulenberg, 1998 ; Masters, 2006 ; Snijder et al, 2013 ; Hartenian et al, 2020 ; Ujike and Taguchi, 2021 ). Classification of viruses within the Nidovirales order is primarily based on several factors, including the organization of the viral genome, the homology of the genome sequence, the antigenic characteristics of the viral proteins, the replication strategy, the structure and physicochemical properties of the virus particle, the natural host range.…”

Section: Classification and Associated Diseases Of Nidoviralesmentioning

confidence: 99%

Classification, replication, and transcription of Nidovirales

Liao,

Wang,

Liao

et al. 2024

Front. Microbiol.

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Nidovirales is one order of RNA virus, with the largest single-stranded positive sense RNA genome enwrapped with membrane envelope. It comprises four families (Arterividae, Mesoniviridae, Roniviridae, and Coronaviridae) and has been circulating in humans and animals for almost one century, posing great threat to livestock and poultry，as well as to public health. Nidovirales shares similar life cycle: attachment to cell surface, entry, primary translation of replicases, viral RNA replication in cytoplasm, translation of viral proteins, virion assembly, budding, and release. The viral RNA synthesis is the critical step during infection, including genomic RNA (gRNA) replication and subgenomic mRNAs (sg mRNAs) transcription. gRNA replication requires the synthesis of a negative sense full-length RNA intermediate, while the sg mRNAs transcription involves the synthesis of a nested set of negative sense subgenomic intermediates by a discontinuous strategy. This RNA synthesis process is mediated by the viral replication/transcription complex (RTC), which consists of several enzymatic replicases derived from the polyprotein 1a and polyprotein 1ab and several cellular proteins. These replicases and host factors represent the optimal potential therapeutic targets. Hereby, we summarize the Nidovirales classification, associated diseases, “replication organelle,” replication and transcription mechanisms, as well as related regulatory factors.

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Recent Progress in Torovirus Molecular Biology

Cited by 13 publications

References 224 publications

Intragenomic rearrangements involving 5′-untranslated region segments in SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses

Intragenomic rearrangements involving 5′-untranslated region segments in SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses

Intragenomic rearrangements of SARS-CoV-2 and other β-coronaviruses

Classification, replication, and transcription of Nidovirales

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