The roles of nucleic acid editing in adaptation of zoonotic viruses to humans

Ratcliff, Jeremy; Simmonds, Peter

doi:10.1016/j.coviro.2023.101326

Cited by 6 publications

(3 citation statements)

References 47 publications

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“…Similarly, an inability of Vif in simian and feline lentiviruses to antagonise APOBECs in heterologous species represented a key factor limiting their host range (46,47). These examples support a more general hypothesis that the failure of viruses in the "wrong" host to antagonise APOBEC editing pathway may be key determinants in their host range (48).…”

Section: Biological Impact Of C->u Mutations In Covid-19mentioning

confidence: 60%

C->U transition biases in SARS-CoV-2 – still rampant four years from the start of the COVID-19 pandemic

Simmonds

2024

Preprint

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The evolution of SARS-CoV2 in the pandemic and post-pandemic periods has been characterised by rapid adaptive changes that confer immune escape and enhanced human-to-human transmissibility. Sequence change is additionally marked by an excess number of C->U transitions suggested as being due to host-mediated genome editing. To investigate how therse influence the evolutionary trajectory of SARS-CoV-2, 2000 high quality, coding complete genome sequences of SARS-CoV-2 variants collected pre-September, 2020, and from each subsequently appearing alpha, delta, BA.1, BA.2, BA.5, XBB, EG, HK and JN.1 lineages were downloaded from NCBI Virus in April, 2024. C->U transitions were the most common substitution during diversification of SARS-CoV-2 lineages over the 4-year observation period. A net loss of C bases and accumulation of U’s occurred at a constant rate of approximately 0.2%-0.25% / decade. C->U transitions occurred in over a quarter of all sites with a C (26.5%; range 20.0%-37.2%), around 5 times more than observed for the other transitions (5.3%-6.8%). In contrast to an approximately random distribution of other transitions across the genome, most C->U substitutions occurred at statistically preferred sites in each lineage. However, only the most C->U polymorphic sites showed evidence for a preferred 5’U context previously associated with APOBEC 3A editing. There was a similarly weak preference for unpaired bases suggesting much less stringent targeting of RNA than mediated by A3 deaminases in DNA editing. Future functional studies are required to determine editing preferences, impacts on replication fitness in vivo of SARS-CoV-2 and other RNA viruses and impact on host tropism.

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Section: Biological Impact Of C->u Mutations In Covid-19mentioning

confidence: 60%

C->U transition biases in SARS-CoV-2 – still rampant four years from the start of the COVID-19 pandemic

Simmonds

2024

Preprint

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“…The RNA editing process is involved in regulating of innate immune responses and may play a key role in antiviral defense [ 44 ]. RNA editing enzymes can act on viruses through two general mechanisms: RNA editing-dependent and RNA editing-independent [ 133 ] (Fig. 6 ).…”

Section: Biological Functions Of Rna Editingmentioning

confidence: 99%

RNA editing enzymes: structure, biological functions and applications

Zhang,

Zhu,

Gao

et al. 2024

Cell Biosci

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With the advancement of sequencing technologies and bioinformatics, over than 170 different RNA modifications have been identified. However, only a few of these modifications can lead to base pair changes, which are called RNA editing. RNA editing is a ubiquitous modification in mammalian transcriptomes and is an important co/posttranscriptional modification that plays a crucial role in various cellular processes. There are two main types of RNA editing events: adenosine to inosine (A-to-I) editing, catalyzed by ADARs on double-stranded RNA or ADATs on tRNA, and cytosine to uridine (C-to-U) editing catalyzed by APOBECs. This article provides an overview of the structure, function, and applications of RNA editing enzymes. We discuss the structural characteristics of three RNA editing enzyme families and their catalytic mechanisms in RNA editing. We also explain the biological role of RNA editing, particularly in innate immunity, cancer biogenesis, and antiviral activity. Additionally, this article describes RNA editing tools for manipulating RNA to correct disease-causing mutations, as well as the potential applications of RNA editing enzymes in the field of biotechnology and therapy.

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“…Almost half were C→U transitions, with the highest proportions in the proximal and distal untranslated regions. Similarly, human APOBEC3 proteins induce C→U transitions in the HIV-1 genome, resulting in antiviral RNA editing and drug resistance ( Ratcliff and Simmonds, 2023 ). Since late 2020, SARS-CoV-2 has exhibited major changes with substantially altered transmissibility and immune escape through the consecutive, independent, and dominant emergence of variants of concern.…”

mentioning

confidence: 99%