ORF-Interrupting Mutations in Monkeypox Virus Genomes from Washington and Ohio, 2022
Monkeypox virus, the causative agent of the 2022 monkeypox outbreak, is a double-stranded DNA virus in the <i>Orthopoxvirus</i> genus of the <i>Poxviridae</i> family. Genes in terminal regions of <i>Orthopoxvirus</i> genomes mostly code for host-pathogen interacti...
| Váldodahkkit: | , , , , , , , , |
|---|---|
| Materiálatiipa: | Artihkal |
| Giella: | English |
| Almmustuhtton: |
MDPI AG
2022-10-01
|
| Ráidu: | Viruses |
| Fáttát: | |
| Liŋkkat: | https://www.mdpi.com/1999-4915/14/11/2393 |
| _version_ | 1827645308945825792 |
|---|---|
| author | Jaydee Sereewit Nicole A. P. Lieberman Hong Xie Shah A. K. Mohamed Bakhash B. Ethan Nunley Benjamin Chung Margaret G. Mills Pavitra Roychoudhury Alexander L. Greninger |
| author_facet | Jaydee Sereewit Nicole A. P. Lieberman Hong Xie Shah A. K. Mohamed Bakhash B. Ethan Nunley Benjamin Chung Margaret G. Mills Pavitra Roychoudhury Alexander L. Greninger |
| author_sort | Jaydee Sereewit |
| collection | DOAJ |
| description | Monkeypox virus, the causative agent of the 2022 monkeypox outbreak, is a double-stranded DNA virus in the <i>Orthopoxvirus</i> genus of the <i>Poxviridae</i> family. Genes in terminal regions of <i>Orthopoxvirus</i> genomes mostly code for host-pathogen interaction proteins and are prone to selective pressure and modification events. Using viral whole genome sequencing, we identified twenty-five total clinical samples with ORF-disrupting mutations, including twenty samples encoding nonsense mutations in MPXVgp001/191 (OPG001), MPXVgp004/188 (OPG015), MPXVgp010 (OPG023), MPXVgp030 (OPG042), MPXVgp159 (OPG0178), or MPXVgp161 (OPG181). Additional mutations include a frameshift leading to an alternative C-terminus in MPXVgp010 (OPG023) and an insertion in an adenine homopolymer at the beginning of the annotated ORF for MPXVgp153 (OPG151), encoding a subunit of the RNA polymerase, suggesting the virus may instead use the start codon that encodes Met9 as annotated. Finally, we detected three samples with large (>900 bp) deletions. These included a 913 bp deletion that truncates the C-terminus of MPXVgp010 (OPG023); a 4205 bp deletion that eliminates MPXVgp012 (OPG025), MPXVgp013 (OPG027), and MPXVgp014 (OPG029) and truncates MPXVgp011 (OPG024; D8L) and MPXVgp015 (OPG030); and a 6881 bp deletion that truncates MPXVgp182 (OPG210) and eliminates putative ORFs MPXVgp184, MPXVgp185 (OPG005), and MPXVgp186, as well as MPXVgp187 (OPG016), and MPXVgp188 (OPG015) from the 3’ ITR only. MPXVgp182 encodes the monkeypox-specific, highly immunogenic surface glycoprotein B21R which has been proposed as a serological target. Overall, we find greater than one-tenth of our sequenced MPXV isolates have at least one gene inactivating mutation and these genes together comprised greater than one-tenth of annotated MPXV genes. Our findings highlight non-essential genes in monkeypox virus that may be evolving as a result of selective pressure in humans, as well as the limitations of targeting them for therapeutics and diagnostic testing. |
| first_indexed | 2024-03-09T18:34:37Z |
| format | Article |
| id | doaj.art-c12f5435b10e491681c1cd62a0c2d0d0 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T18:34:37Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-c12f5435b10e491681c1cd62a0c2d0d02023-11-24T07:16:28ZengMDPI AGViruses1999-49152022-10-011411239310.3390/v14112393ORF-Interrupting Mutations in Monkeypox Virus Genomes from Washington and Ohio, 2022Jaydee Sereewit0Nicole A. P. Lieberman1Hong Xie2Shah A. K. Mohamed Bakhash3B. Ethan Nunley4Benjamin Chung5Margaret G. Mills6Pavitra Roychoudhury7Alexander L. Greninger8Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USADepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USADepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USADepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USADepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USADepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USADepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USADepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USADepartment of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USAMonkeypox virus, the causative agent of the 2022 monkeypox outbreak, is a double-stranded DNA virus in the <i>Orthopoxvirus</i> genus of the <i>Poxviridae</i> family. Genes in terminal regions of <i>Orthopoxvirus</i> genomes mostly code for host-pathogen interaction proteins and are prone to selective pressure and modification events. Using viral whole genome sequencing, we identified twenty-five total clinical samples with ORF-disrupting mutations, including twenty samples encoding nonsense mutations in MPXVgp001/191 (OPG001), MPXVgp004/188 (OPG015), MPXVgp010 (OPG023), MPXVgp030 (OPG042), MPXVgp159 (OPG0178), or MPXVgp161 (OPG181). Additional mutations include a frameshift leading to an alternative C-terminus in MPXVgp010 (OPG023) and an insertion in an adenine homopolymer at the beginning of the annotated ORF for MPXVgp153 (OPG151), encoding a subunit of the RNA polymerase, suggesting the virus may instead use the start codon that encodes Met9 as annotated. Finally, we detected three samples with large (>900 bp) deletions. These included a 913 bp deletion that truncates the C-terminus of MPXVgp010 (OPG023); a 4205 bp deletion that eliminates MPXVgp012 (OPG025), MPXVgp013 (OPG027), and MPXVgp014 (OPG029) and truncates MPXVgp011 (OPG024; D8L) and MPXVgp015 (OPG030); and a 6881 bp deletion that truncates MPXVgp182 (OPG210) and eliminates putative ORFs MPXVgp184, MPXVgp185 (OPG005), and MPXVgp186, as well as MPXVgp187 (OPG016), and MPXVgp188 (OPG015) from the 3’ ITR only. MPXVgp182 encodes the monkeypox-specific, highly immunogenic surface glycoprotein B21R which has been proposed as a serological target. Overall, we find greater than one-tenth of our sequenced MPXV isolates have at least one gene inactivating mutation and these genes together comprised greater than one-tenth of annotated MPXV genes. Our findings highlight non-essential genes in monkeypox virus that may be evolving as a result of selective pressure in humans, as well as the limitations of targeting them for therapeutics and diagnostic testing.https://www.mdpi.com/1999-4915/14/11/2393monkeypox virusserologyessential genegenomic deletionB21R |
| spellingShingle | Jaydee Sereewit Nicole A. P. Lieberman Hong Xie Shah A. K. Mohamed Bakhash B. Ethan Nunley Benjamin Chung Margaret G. Mills Pavitra Roychoudhury Alexander L. Greninger ORF-Interrupting Mutations in Monkeypox Virus Genomes from Washington and Ohio, 2022 Viruses monkeypox virus serology essential gene genomic deletion B21R |
| title | ORF-Interrupting Mutations in Monkeypox Virus Genomes from Washington and Ohio, 2022 |
| title_full | ORF-Interrupting Mutations in Monkeypox Virus Genomes from Washington and Ohio, 2022 |
| title_fullStr | ORF-Interrupting Mutations in Monkeypox Virus Genomes from Washington and Ohio, 2022 |
| title_full_unstemmed | ORF-Interrupting Mutations in Monkeypox Virus Genomes from Washington and Ohio, 2022 |
| title_short | ORF-Interrupting Mutations in Monkeypox Virus Genomes from Washington and Ohio, 2022 |
| title_sort | orf interrupting mutations in monkeypox virus genomes from washington and ohio 2022 |
| topic | monkeypox virus serology essential gene genomic deletion B21R |
| url | https://www.mdpi.com/1999-4915/14/11/2393 |
| work_keys_str_mv | AT jaydeesereewit orfinterruptingmutationsinmonkeypoxvirusgenomesfromwashingtonandohio2022 AT nicoleaplieberman orfinterruptingmutationsinmonkeypoxvirusgenomesfromwashingtonandohio2022 AT hongxie orfinterruptingmutationsinmonkeypoxvirusgenomesfromwashingtonandohio2022 AT shahakmohamedbakhash orfinterruptingmutationsinmonkeypoxvirusgenomesfromwashingtonandohio2022 AT bethannunley orfinterruptingmutationsinmonkeypoxvirusgenomesfromwashingtonandohio2022 AT benjaminchung orfinterruptingmutationsinmonkeypoxvirusgenomesfromwashingtonandohio2022 AT margaretgmills orfinterruptingmutationsinmonkeypoxvirusgenomesfromwashingtonandohio2022 AT pavitraroychoudhury orfinterruptingmutationsinmonkeypoxvirusgenomesfromwashingtonandohio2022 AT alexanderlgreninger orfinterruptingmutationsinmonkeypoxvirusgenomesfromwashingtonandohio2022 |