Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus

Rivera-Calzada, Ángel; Arribas-Bosacoma, Raquel; Ruiz‐Ramos, Alba; Escudero-Bravo, Paloma; Boskovic, Jasminka; Fernández-Leiro, Rafael; Oliver, Antony W.; Pearl, Laurence H.; Llorca, Óscar

doi:10.1038/s41467-022-34843-z

Cited by 9 publications

(1 citation statement)

References 43 publications

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“…Domains of unknown function (DUFs) are not automatically detected by the genome2bgc module. However, we do include DUFs that have been previously linked to the biosynthesis of RiPPs, such as DUF4135 for the synthesis of lanthipeptides 61 .…”

Section: Methodsmentioning

confidence: 99%

HypoRiPPAtlas as an Atlas of hypothetical natural products for mass spectrometry database search

et al. 2023

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Recent analyses of public microbial genomes have found over a million biosynthetic gene clusters, the natural products of the majority of which remain unknown. Additionally, GNPS harbors billions of mass spectra of natural products without known structures and biosynthetic genes. We bridge the gap between large-scale genome mining and mass spectral datasets for natural product discovery by developing HypoRiPPAtlas, an Atlas of hypothetical natural product structures, which is ready-to-use for in silico database search of tandem mass spectra. HypoRiPPAtlas is constructed by mining genomes using seq2ripp, a machine-learning tool for the prediction of ribosomally synthesized and post-translationally modified peptides (RiPPs). In HypoRiPPAtlas, we identify RiPPs in microbes and plants. HypoRiPPAtlas could be extended to other natural product classes in the future by implementing corresponding biosynthetic logic. This study paves the way for large-scale explorations of biosynthetic pathways and chemical structures of microbial and plant RiPP classes.

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Section: Methodsmentioning

confidence: 99%

HypoRiPPAtlas as an Atlas of hypothetical natural products for mass spectrometry database search

et al. 2023

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The monkeypox virus-host interplays

Yi,

Lei,

et al. 2024

Cell Insight

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Selective events at individual sites underlie the evolution of monkeypox virus clades

et al. 2023

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In endemic regions (West Africa and the Congo Basin), the genetic diversity of monkeypox virus (MPXV) is geographically structured into two major clades (clade I and II) that differ in virulence and host associations. Clade IIb is closely related to the B.1 lineage, which is dominating a worldwide outbreak initiated in 2022. Lineage B.1 has however accumulated mutations of unknown significance that most likely result from APOBEC3 (apolipoprotein B mRNA editing catalytic polypeptide-like 3) editing. We applied a population genetics-phylogenetics approach to investigate the evolution of MPXV during historical viral spread in Africa and to infer the distribution of fitness effects. We observed a high preponderance of codons evolving under strong purifying selection, particularly in viral genes involved in morphogenesis and replication or transcription. However, signals of positive selection were also detected and were enriched in genes involved in immunomodulation and/or virulence. In particular, several genes showing evidence of positive selection were found to hijack different steps of the cellular pathway that senses cytosolic DNA. Also, a few selected sites in genes that are not directly involved in immunomodulation are suggestive of antibody escape or other immuno-mediated pressures. Because orthopoxvirus host range is primarily determined by the interaction with the host immune system, we suggest that the positive selection signals represent signatures of host adaptation and contribute to the different virulence of clade I and II MPXV. We also used the calculated selection coefficients to infer the effects of mutations that define the predominant hMPXV1 lineage B.1, as well as the changes that have been accumulating during the worldwide outbreak. Results indicated that a proportion of deleterious mutations were purged from the predominant outbreak lineage, whose spread was not driven by the presence of beneficial changes. Polymorphic mutations with a predicted beneficial effect on fitness are few and have a low frequency. It remains to be determined whether they have any significance for ongoing virus evolution.

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Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus

Cited by 9 publications

References 43 publications

HypoRiPPAtlas as an Atlas of hypothetical natural products for mass spectrometry database search

HypoRiPPAtlas as an Atlas of hypothetical natural products for mass spectrometry database search

The monkeypox virus-host interplays

Selective events at individual sites underlie the evolution of monkeypox virus clades

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