{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:15:00Z","timestamp":1793045700788,"version":"4.5.0"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T00:00:00Z","timestamp":1684540800000},"content-version":"vor","delay-in-days":139,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RC2022"],"award-info":[{"award-number":["RC2022"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In endemic regions (West Africa and the Congo Basin), the genetic diversity of monkeypox virus (MPXV) is geographically structured into two major clades (Clades 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 apolipoprotein B mRNA editing catalytic polypeptide-like 3 (APOBEC3) editing. We applied a population genetics\u2014phylogenetics 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 immune-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 MPXVs. We also used the calculated selection coefficients to infer the effects of mutations that define the predominant human MPXV1 (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.<\/jats:p>","DOI":"10.1093\/ve\/vead031","type":"journal-article","created":{"date-parts":[[2023,5,21]],"date-time":"2023-05-21T00:57:30Z","timestamp":1684630650000},"source":"Crossref","is-referenced-by-count":13,"title":["Selective events at individual sites underlie the evolution of\u00a0monkeypox virus clades"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7259-9230","authenticated-orcid":false,"given":"Cristian","family":"Molteni","sequence":"first","affiliation":[{"name":"Scientific Institute IRCCS E. MEDEA, Bioinformatics , Via don Luigi Monza, Bosisio Parini 23842, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-5352","authenticated-orcid":false,"given":"Diego","family":"Forni","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS E. MEDEA, Bioinformatics , Via don Luigi Monza, Bosisio Parini 23842, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-3532","authenticated-orcid":false,"given":"Rachele","family":"Cagliani","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS E. MEDEA, Bioinformatics , Via don Luigi Monza, Bosisio Parini 23842, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Arrigoni","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milan-Bicocca , Piazza della scienza, Milan 20126, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Pozzoli","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS E. MEDEA, Bioinformatics , Via don Luigi Monza, Bosisio Parini 23842, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"De Gioia","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milan-Bicocca , Piazza della scienza, Milan 20126, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Sironi","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS E. MEDEA, Bioinformatics , Via don Luigi Monza, Bosisio Parini 23842, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,20]]},"reference":[{"key":"2023060918365133800_R1","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.7326\/M22-1581","article-title":"A Novel International Monkeypox Outbreak","volume":"175","author":"Adalja","year":"2022","journal-title":"Annals of Internal Medicine"},{"key":"2023060918365133800_R2","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/S1473-3099(22)00228-6","article-title":"NHS England High Consequence Infectious Diseases (Airborne) Network. Clinical Features and\u00a0Management of\u00a0Human Monkeypox: A Retrospective Observational Study in\u00a0the UK","volume":"22","author":"Adler","year":"2022","journal-title":"The Lancet Infectious Diseases"},{"key":"2023060918365133800_R3","doi-asserted-by":"crossref","DOI":"10.21105\/joss.03773","article-title":"Nextclade: Clade Assignment, Mutation Calling and\u00a0Quality Control for\u00a0Viral Genomes","volume":"6","author":"Aksamentov","year":"2021","journal-title":"The Journal of Open Source Software"},{"key":"2023060918365133800_R4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004123","article-title":"T Cell Inactivation by Poxviral B22 Family Proteins Increases Viral Virulence","volume":"10","author":"Alzhanova","year":"2014","journal-title":"PLoS Pathogens"},{"key":"2023060918365133800_R6","doi-asserted-by":"crossref","first-page":"W580","DOI":"10.1093\/nar\/gks498","article-title":"FastML: A Web Server for\u00a0Probabilistic Reconstruction of\u00a0Ancestral Sequences","volume":"40","author":"Ashkenazy","year":"2012","journal-title":"Nucleic Acids Research"},{"key":"2023060918365133800_R7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev.physchem.51.1.129","article-title":"Generalized Born Models of\u00a0Macromolecular Solvation Effects","volume":"51","author":"Bashford","year":"2000","journal-title":"Annual Review of Physical Chemistry"},{"key":"2023060918365133800_R8","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-92315-8","article-title":"Genomic History of\u00a0Human Monkey Pox Infections in\u00a0the Central African Republic between 2001 and\u00a02018","volume":"11","author":"Berthet","year":"2021","journal-title":"Scientific Reports"},{"key":"2023060918365133800_R9","article-title":"Epidemiological Trends and\u00a0Clinical Features of\u00a0the Ongoing Monkeypox Epidemic: A Preliminary Pooled Data Analysis and\u00a0Literature Review","volume":"95","author":"Bragazzi","year":"2022","journal-title":"Journal of Medical Virology"},{"key":"2023060918365133800_R10","doi-asserted-by":"crossref","first-page":"9986","DOI":"10.1128\/JVI.01233-15","article-title":"Experimental Evolution Identifies Vaccinia Virus Mutations in\u00a0A24R and\u00a0A35R That Antagonize the Protein Kinase R Pathway and\u00a0Accompany Collapse of\u00a0an Extragenic Gene Amplification","volume":"89","author":"Brennan","year":"2015","journal-title":"Journal of Virology"},{"key":"2023060918365133800_R11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0010141","article-title":"The Changing Epidemiology of\u00a0Human Monkeypox-A Potential Threat? A Systematic Review","volume":"16","author":"Bunge","year":"2022","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"2023060918365133800_R12","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.virol.2014.03.019","article-title":"Initial Characterization of\u00a0Vaccinia Virus B4 Suggests a Role in\u00a0Virus Spread","volume":"456-457","author":"Burles","year":"2014","journal-title":"Virology"},{"key":"2023060918365133800_R13","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1084\/jem.20062026","article-title":"Zoonotic Orthopoxviruses Encode a High-affinity Antagonist of\u00a0NKG2D","volume":"204","author":"Campbell","year":"2007","journal-title":"Journal of Experimental Medicine"},{"key":"2023060918365133800_R15","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.virol.2005.05.030","article-title":"Virulence Differences between Monkeypox Virus Isolates from West Africa and\u00a0the Congo Basin","volume":"340","author":"Chen","year":"2005","journal-title":"Virology"},{"key":"2023060918365133800_R16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.0040022","article-title":"Inhibition of\u00a0IkappaB Kinase by Vaccinia Virus Virulence Factor B14","volume":"4","author":"Chen","year":"2008","journal-title":"PLoS Pathogens"},{"key":"2023060918365133800_R17","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1099\/vir.0.81736-0","article-title":"Vaccinia Virus Strain Western Reserve Protein B14 Is an Intracellular Virulence Factor","volume":"87","author":"Chen","year":"2006","journal-title":"Journal of General Virology"},{"key":"2023060918365133800_R18","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.3201\/eid2805.220292","article-title":"Imported Monkeypox from International Traveler, Maryland, USA, 2021","volume":"28","author":"Costello","year":"2022","journal-title":"Emerging Infectious Diseases"},{"key":"2023060918365133800_R19","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1021\/ci900320p","article-title":"Prediction of\u00a0Potency of\u00a0Protease Inhibitors Using Free Energy Simulations with Polarizable Quantum Mechanics-based Ligand Charges and\u00a0a Hybrid Water Model","volume":"49","author":"Das","year":"2009","journal-title":"Journal of Chemical Information and Modeling"},{"key":"2023060918365133800_R20","doi-asserted-by":"crossref","first-page":"11724","DOI":"10.1128\/JVI.79.18.11724-11733.2005","article-title":"Vaccinia Virus H3L Envelope Protein Is a Major Target of\u00a0Neutralizing Antibodies in\u00a0Humans and\u00a0Elicits Protection against Lethal Challenge in\u00a0Mice","volume":"79","author":"Davies","year":"2005","journal-title":"Journal of Virology"},{"key":"2023060918365133800_R21","doi-asserted-by":"crossref","DOI":"10.3390\/v9100283","article-title":"Assessing Monkeypox Virus Prevalence in\u00a0Small Mammals at the Human-Animal Interface in\u00a0the Democratic Republic of\u00a0the Congo","volume":"9","author":"Doty","year":"2017","journal-title":"Viruses"},{"key":"2023060918365133800_R22","article-title":"Analyses of\u00a0Evolutionary Dynamics in\u00a0Viruses Are Hindered by a Time-dependent Bias in\u00a0Rate Estimates","volume":"281","author":"Duchene","year":"2014","journal-title":"Proceedings Biological Sciences"},{"key":"2023060918365133800_R23","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41586-019-0928-6","article-title":"Viral and\u00a0Metazoan Poxins are cGAMP-specific Nucleases That Restrict cGAS-STING Signalling","volume":"566","author":"Eaglesham","year":"2019","journal-title":"Nature"},{"key":"2023060918365133800_R24","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-019-1832-y","article-title":"OrthoFinder: Phylogenetic Orthology Inference for\u00a0Comparative Genomics","volume":"20","author":"Emms","year":"2019","journal-title":"Genome Biology"},{"key":"2023060918365133800_R25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004130","article-title":"Further Assessment of\u00a0Monkeypox Virus Infection in\u00a0Gambian Pouched Rats (Cricetomys gambianus) Using in\u00a0Vivo Bioluminescent Imaging","volume":"9","author":"Falendysz","year":"2015","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"2023060918365133800_R14","article-title":"Characterization of\u00a0Monkeypox Virus Infection in\u00a0African Rope Squirrels (Funisciurus sp.)","volume":"11","year":"2017","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"2023060918365133800_R26","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.00047","article-title":"DNA-PK Is a DNA Sensor for\u00a0IRF-3-dependent Innate Immunity","volume":"1","author":"Ferguson","year":"2012","journal-title":"Elife"},{"key":"2023060918365133800_R27","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1093\/infdis\/jiac298","article-title":"Geographic Structuring and\u00a0Divergence Time Frame of\u00a0Monkeypox Virus in\u00a0the Endemic Region","volume":"227","author":"Forni","year":"2022","journal-title":"The Journal of Infectious Diseases"},{"key":"2023060918365133800_R47","article-title":"Monkeypox Virus: The Changing Facets of\u00a0a Zoonotic Pathogen","volume":"105","year":"2022","journal-title":"Infection, Genetics and Evolution"},{"key":"2023060918365133800_R5","article-title":"An APOBEC3 Mutational Signature in\u00a0the Genomes of\u00a0Human-Infecting Orthopoxviruses","volume":"8","year":"2023","journal-title":"mSphere"},{"key":"2023060918365133800_R28","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1126\/science.add4153","article-title":"Multiple Lineages of\u00a0Monkeypox Virus Detected in\u00a0the United States, 2021-2022","volume":"378","author":"Gigante","year":"2022","journal-title":"Science"},{"key":"2023060918365133800_R29","doi-asserted-by":"crossref","DOI":"10.1016\/j.nmni.2023.101102","article-title":"Emergence, Phylogeography, and\u00a0Adaptive Evolution of\u00a0Mpox Virus","volume":"52","author":"Guan","year":"2023","journal-title":"New Microbes and New Infections"},{"key":"2023060918365133800_R30","first-page":"113","article-title":"Estimating Maximum Likelihood Phylogenies with PhyML","volume":"537","author":"Guindon","year":"2009","journal-title":"Methods in Nolecular Biology (Clifton, N.J.)"},{"key":"2023060918365133800_R31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1005203","article-title":"Overlapping Patterns of\u00a0Rapid Evolution in\u00a0the Nucleic Acid Sensors cGAS and\u00a0OAS1 Suggest a Common Mechanism of\u00a0Pathogen Antagonism and\u00a0Escape","volume":"11","author":"Hancks","year":"2015","journal-title":"PLoS Genetics"},{"key":"2023060918365133800_R32","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3001769","article-title":"Urgent Need for\u00a0a Non-discriminatory and\u00a0Non-stigmatizing Nomenclature for\u00a0Monkeypox Virus","volume":"20","author":"Happi","year":"2022","journal-title":"PLoS Biology"},{"key":"2023060918365133800_R33","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.3390\/v2091933","article-title":"Orthopoxvirus Genome Evolution: The Role of\u00a0Gene Loss","volume":"2","author":"Hendrickson","year":"2010","journal-title":"Viruses"},{"key":"2023060918365133800_R35","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens11080875","article-title":"Poxviral ANKR\/F-box Proteins: Substrate Adapters for\u00a0Ubiquitylation and\u00a0More","volume":"11","author":"Ingham","year":"2022","journal-title":"Pathogens"},{"key":"2023060918365133800_R36","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1038\/s41591-022-01907-y","article-title":"Phylogenomic Characterization and\u00a0Signs of\u00a0Microevolution in\u00a0the 2022 Multi-country Outbreak of\u00a0Monkeypox Virus","volume":"28","author":"Isidro","year":"2022","journal-title":"Nature Medicine"},{"key":"2023060918365133800_R37","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein Structure Prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"2023060918365133800_R38","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT Multiple Sequence Alignment Software Version 7: Improvements in\u00a0Performance and\u00a0Usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Molecular Biology and Evolution"},{"key":"2023060918365133800_R39","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/j.chom.2021.05.009","article-title":"Vaccinia Virus E3 Prevents Sensing of\u00a0Z-RNA to Block ZBP1-dependent Necroptosis","volume":"29","author":"Koehler","year":"2021","journal-title":"Cell Host & Microbe"},{"key":"2023060918365133800_R40","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1006111","article-title":"Genetic Drift, Purifying Selection and\u00a0Vector Genotype Shape Dengue Virus Intra-host Genetic Diversity in\u00a0Mosquitoes","volume":"12","author":"Lequime","year":"2016","journal-title":"PLoS Genetics"},{"key":"2023060918365133800_R41","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1099\/vir.0.81215-0","article-title":"A Tale of\u00a0Two Clades: Monkeypox Viruses","volume":"86","author":"Likos","year":"2005","journal-title":"Journal of General Virology"},{"key":"2023060918365133800_R42","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.immuni.2020.11.020","article-title":"A Class of\u00a0Viral Inducer of\u00a0Degradation of\u00a0the Necroptosis Adaptor RIPK3 Regulates Virus-induced Inflammation","volume":"54","author":"Liu","year":"2021","journal-title":"Immunity"},{"key":"2023060918365133800_R43","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1007\/s11262-017-1504-5","article-title":"Cellular Interactome Analysis of\u00a0Vaccinia Virus K7 Protein Identifies Three Transport Machineries as Binding Partners for\u00a0K7","volume":"53","author":"Li","year":"2017","journal-title":"Virus Genes"},{"key":"2023060918365133800_R44","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1074\/jbc.M117.814541","article-title":"Structure-function Characterization of\u00a0Three Human Antibodies Targeting the Vaccinia Virus Adhesion Molecule D8","volume":"293","author":"Matho","year":"2018","journal-title":"Journal of Biological Chemistry"},{"key":"2023060918365133800_R45","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/infdis\/jiaa559","article-title":"Exportation of\u00a0Monkeypox Virus from the African Continent","volume":"225","author":"Mauldin","year":"2022","journal-title":"The Journal of Infectious Diseases"},{"key":"2023060918365133800_R46","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making Protein Folding Accessible to All","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nature Methods"},{"key":"2023060918365133800_R48","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1093\/gbe\/evv046","article-title":"OASes and\u00a0STING: Adaptive Evolution in\u00a0Concert","volume":"7","author":"Mozzi","year":"2015","journal-title":"Genome Biology and Evolution"},{"key":"2023060918365133800_R49","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/S1473-3099(19)30537-7","article-title":"A Case of\u00a0Imported Monkeypox in\u00a0Singapore","volume":"19","author":"Ng","year":"2019","journal-title":"The Lancet Infectious Diseases"},{"key":"2023060918365133800_R50","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1001\/jama.2022.12513","article-title":"The WHO Declaration of\u00a0Monkeypox as a Global Public Health Emergency","volume":"328","author":"Nuzzo","year":"2022","journal-title":"Jama"},{"key":"2023060918365133800_R51","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1016\/j.str.2009.09.005","article-title":"Structural Basis for\u00a0Targeting of\u00a0Human RNA Helicase DDX3 by Poxvirus Protein K7","volume":"17","author":"Oda","year":"2009","journal-title":"Structure"},{"key":"2023060918365133800_R52","article-title":"Putative APOBEC3 Deaminase Editing in\u00a0MPXV as Evidence for\u00a0Sustained Human Transmission since at Least 2016","author":"O\u2019Toole","year":"2023","journal-title":"BioRXiv"},{"key":"2023060918365133800_R53","doi-asserted-by":"crossref","first-page":"5405","DOI":"10.1093\/molbev\/msab256","article-title":"Evolutionary Profile for\u00a0(Host and\u00a0Viral) MLKL Indicates Its Activities as a Battlefront for\u00a0Extensive Counteradaptation","volume":"38","author":"Palmer","year":"2021","journal-title":"Molecular Biology and Evolution"},{"key":"2023060918365133800_R54","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/s41564-020-0706-0","article-title":"Monkeypox Virus Emergence in\u00a0Wild Chimpanzees Reveals Distinct Clinical Outcomes and\u00a0Viral Diversity","volume":"5","author":"Patrono","year":"2020","journal-title":"Nature Microbiology"},{"key":"2023060918365133800_R55","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003649","article-title":"A Mechanism for\u00a0the Inhibition of\u00a0DNA-PK-mediated DNA Sensing by A Virus","volume":"9","author":"Peters","year":"2013","journal-title":"PLoS Pathogens"},{"key":"2023060918365133800_R56","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1006\/viro.1999.0116","article-title":"Vaccinia Virus Gene B7R Encodes an 18-kDa Protein that Is Resident in\u00a0the Endoplasmic Reticulum and\u00a0Affects Virus Virulence","volume":"267","author":"Price","year":"2000","journal-title":"Virology"},{"key":"2023060918365133800_R57","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0009490","article-title":"FastTree 2\u2014approximately Maximum-likelihood Trees for\u00a0Large Alignments","volume":"5","author":"Price","year":"2010","journal-title":"PLoS One"},{"key":"2023060918365133800_R58","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/molbev\/msm001","article-title":"Phylogenetic Evidence for\u00a0Deleterious Mutation Load in\u00a0RNA Viruses and\u00a0Its Contribution to Viral Evolution","volume":"24","author":"Pybus","year":"2007","journal-title":"Molecular Biology and Evolution"},{"key":"2023060918365133800_R59","doi-asserted-by":"crossref","first-page":"509","DOI":"10.15585\/mmwr.mm7114a1","article-title":"Monkeypox in\u00a0a Traveler Returning from Nigeria - Dallas, Texas, July 2021","volume":"71","author":"Rao","year":"2022","journal-title":"MMWR. Morbidity and Mortality Weekly Report"},{"key":"2023060918365133800_R60","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.virol.2009.11.008","article-title":"Vaccinia Virus A35R Inhibits MHC Class II Antigen Presentation","volume":"397","author":"Rehm","year":"2010","journal-title":"Virology"},{"key":"2023060918365133800_R61","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1086\/505880","article-title":"Clinical Manifestations of\u00a0Human Monkeypox Influenced by Route of\u00a0Infection","volume":"194","author":"Reynolds","year":"2006","journal-title":"The Journal of Infectious Diseases"},{"key":"2023060918365133800_R62","doi-asserted-by":"crossref","first-page":"16262","DOI":"10.1073\/pnas.1005769107","article-title":"Major Increase in\u00a0Human Monkeypox Incidence 30 Years after Smallpox Vaccination Campaigns Cease in\u00a0the Democratic Republic of\u00a0Congo","volume":"107","author":"Rimoin","year":"2010","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"2023060918365133800_R63","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-022-34843-z","article-title":"Structural Basis for\u00a0the Inactivation of\u00a0Cytosolic DNA Sensing by the Vaccinia Virus","volume":"13","author":"Rivera-Calzada","year":"2022","journal-title":"Nature Communications"},{"key":"2023060918365133800_R64","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1128\/JVI.80.1.306-313.2006","article-title":"Characterization of\u00a0the Vaccinia Virus A35R Protein and\u00a0Its Role in\u00a0Virulence","volume":"80","author":"Roper","year":"2006","journal-title":"Journal of Virology"},{"key":"2023060918365133800_R65","doi-asserted-by":"crossref","first-page":"e01385","DOI":"10.1128\/JVI.01385-17","article-title":"Vaccinia Virus Encodes a Novel Inhibitor of\u00a0Apoptosis That Associates with the Apoptosome","volume":"91","author":"Ryerson","year":"2017","journal-title":"Journal of Virology"},{"key":"2023060918365133800_R66","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1038\/emboj.2008.143","article-title":"Viral Targeting of\u00a0DEAD Box Protein 3 Reveals Its Role in\u00a0TBK1\/IKKepsilon-mediated IRF Activation","volume":"27","author":"Schr\u00f6der","year":"2008","journal-title":"The EMBO Journal"},{"key":"2023060918365133800_R67","doi-asserted-by":"crossref","first-page":"W7","DOI":"10.1093\/nar\/gkv318","article-title":"GUIDANCE2: Accurate Detection of\u00a0Unreliable Alignment Regions Accounting for\u00a0the Uncertainty of\u00a0Multiple Parameters","volume":"43","author":"Sela","year":"2015","journal-title":"Nucleic Acids Research"},{"key":"2023060918365133800_R68","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.virol.2008.01.009","article-title":"A Conserved Poxvirus NlpC\/P60 Superfamily Protein Contributes to Vaccinia Virus Virulence in\u00a0Mice but Not to Replication in\u00a0Cell Culture","volume":"374","author":"Senkevich","year":"2008","journal-title":"Virology"},{"key":"2023060918365133800_R69","article-title":"Molecular Evolution of\u00a0Protein Sequences and\u00a0Codon Usage in\u00a0Monkeypox Viruses","author":"Shan","year":"2022","journal-title":"bioRxiv"},{"key":"2023060918365133800_R70","doi-asserted-by":"crossref","first-page":"5077","DOI":"10.1016\/j.vaccine.2020.04.062","article-title":"Human Monkeypox - after 40 Years, an Unintended Consequence of\u00a0Smallpox Eradication","volume":"38","author":"Simpson","year":"2020","journal-title":"Vaccine"},{"key":"2023060918365133800_R71","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nrg3905","article-title":"Evolutionary Insights into Host-pathogen Interactions from Mammalian Sequence Data","volume":"16","author":"Sironi","year":"2015","journal-title":"Nature Reviews. Genetics"},{"key":"2023060918365133800_R72","doi-asserted-by":"crossref","DOI":"10.3389\/fpubh.2018.00241","article-title":"Emergence of\u00a0Monkeypox as the Most Important Orthopoxvirus Infection in\u00a0Humans","volume":"6","author":"Sklenovsk\u00e1","year":"2018","journal-title":"Frontiers in Public Health"},{"key":"2023060918365133800_R73","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.virol.2009.10.025","article-title":"Vaccinia Virus A43R Gene Encodes an Orthopoxvirus-specific Late Non-virion Type-1 Membrane Protein That Is Dispensable for\u00a0Replication but Enhances Intradermal Lesion Formation","volume":"396","author":"Sood","year":"2010","journal-title":"Virology"},{"key":"2023060918365133800_R74","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.cell.2011.11.031","article-title":"Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of\u00a0RIP3 Kinase","volume":"148","author":"Sun","year":"2012","journal-title":"Cell"},{"key":"2023060918365133800_R75","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0173056","article-title":"The Vaccinia Virus K7 Protein Promotes Histone Methylation Associated with Heterochromatin Formation","volume":"12","author":"Teferi","year":"2017","journal-title":"PLoS One"},{"key":"2023060918365133800_R76","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1056\/NEJMoa2207323","article-title":"Monkeypox Virus Infection in\u00a0Humans across 16 Countries - April-June 2022","volume":"387","author":"Thornhill","year":"2022","journal-title":"New England Journal of Medicine"},{"key":"2023060918365133800_R77","doi-asserted-by":"crossref","DOI":"10.1098\/rsos.171089","article-title":"Ghosts of\u00a0Infections Past: Using Archival Samples to Understand a Century of\u00a0Monkeypox Virus Prevalence among Host Communities across Space and\u00a0Time","volume":"5","author":"Tiee","year":"2018","journal-title":"Royal Society Open Science"},{"key":"2023060918365133800_R78","doi-asserted-by":"crossref","first-page":"5059","DOI":"10.1128\/JVI.80.10.5059-5064.2006","article-title":"Double-stranded RNA Is Produced by Positive-strand RNA Viruses and\u00a0DNA Viruses but Not in\u00a0Detectable\u00a0Amounts by Negative-strand RNA Viruses","volume":"80","author":"Weber","year":"2006","journal-title":"Journal of Virology"},{"key":"2023060918365133800_R79","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1093\/molbev\/msr170","article-title":"Purifying Selection Can Obscure the Ancient Age of\u00a0Viral Lineages","volume":"28","author":"Wertheim","year":"2011","journal-title":"Molecular Biology and Evolution"},{"key":"2023060918365133800_R80","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1002395","article-title":"A Population Genetics-phylogenetics Approach to Inferring Natural Selection in\u00a0Coding Sequences","volume":"7","author":"Wilson","year":"2011","journal-title":"PLoS Genetics"},{"key":"2023060918365133800_R81","doi-asserted-by":"crossref","DOI":"10.1186\/s13321-017-0246-7","article-title":"Efficient Conformational Ensemble Generation of\u00a0Protein-bound Peptides","volume":"9","author":"Yan","year":"2017","journal-title":"Journal of Cheminformatics"},{"key":"2023060918365133800_R82","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/S1473-3099(19)30294-4","article-title":"CDC Monkeypox Outbreak Team. Outbreak of\u00a0Human Monkeypox in\u00a0Nigeria in\u00a02017-18: A Clinical and\u00a0Epidemiological Report","volume":"19","author":"Yinka-Ogunleye","year":"2019","journal-title":"The Lancet Infectious Diseases"},{"key":"2023060918365133800_R83","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2022.1083234","article-title":"Evolutionary Dissection of\u00a0Monkeypox Virus: Positive Darwinian Selection Drives the Adaptation of\u00a0Virus-host Interaction Proteins","volume":"12","author":"Zhan","year":"2023","journal-title":"Frontiers in Cellular and Infection Microbiology"},{"key":"2023060918365133800_R84","doi-asserted-by":"crossref","first-page":"W443","DOI":"10.1093\/nar\/gky357","article-title":"HPEPDOCK: A Web Server for\u00a0Blind Peptide-protein Docking Based on\u00a0a Hierarchical Algorithm","volume":"46","author":"Zhou","year":"2018","journal-title":"Nucleic Acids Research"},{"key":"2023060918365133800_R34","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1021\/acs.jcim.8b00142","article-title":"Hierarchical Flexible Peptide Docking by Conformer Generation and\u00a0Ensemble Docking of\u00a0Peptides","volume":"58","year":"2018","journal-title":"Journal of Chemical Information and Modeling"}],"container-title":["Virus Evolution"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ve\/advance-article-pdf\/doi\/10.1093\/ve\/vead031\/50412595\/vead031.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ve\/article-pdf\/9\/1\/vead031\/50564144\/vead031.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ve\/article-pdf\/9\/1\/vead031\/50564144\/vead031.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T18:38:15Z","timestamp":1686335895000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ve\/article\/doi\/10.1093\/ve\/vead031\/7175024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":84,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,6,9]]}},"URL":"https:\/\/doi.org\/10.1093\/ve\/vead031","relation":{},"ISSN":["2057-1577"],"issn-type":[{"value":"2057-1577","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,1]]},"published":{"date-parts":[[2023,1,1]]},"article-number":"vead031"}}