A functional approach to analyze the genetic basis for differences in virulence of monkeypox virus clades
Mpox, the disease caused by monkeypox virus (MPXV) is increasing in Africa and in 2022 spread to more than 100 countries sickening more than 100,000 individuals. Four clades of MPXV have been recognized with differences in severity of disease and extent of human-to-human transmission. Determination...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
|
| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2025.2456144 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832542266518929408 |
|---|---|
| author | Patricia L. Earl Jeffrey L. Americo Sara Reynolds Wei Xiao Catherine Cotter Bernard Moss |
| author_facet | Patricia L. Earl Jeffrey L. Americo Sara Reynolds Wei Xiao Catherine Cotter Bernard Moss |
| author_sort | Patricia L. Earl |
| collection | DOAJ |
| description | Mpox, the disease caused by monkeypox virus (MPXV) is increasing in Africa and in 2022 spread to more than 100 countries sickening more than 100,000 individuals. Four clades of MPXV have been recognized with differences in severity of disease and extent of human-to-human transmission. Determination of the genetic basis for these differences could help to develop improved therapeutics and vaccines. The Castaneous (CAST) mouse is highly susceptible to MPXV and virulence differences of MPXV clades are statistically significant mimicking their relative severities in humans. The present study was intended to evaluate the CAST mouse as a model for investigating genomic differences by replacing genes of Zaire-1979 005 (Z-79) clade Ia MPXV with homologous gene sequences of the less virulent and less transmissible USA-2003 clade IIa MPXV. The expectation was that some gene replacements would reduce the virulence of Z-79 chimera. Recombinant viruses expressing firefly luciferase were constructed in which partially overlapping Z-79 DNA segments of 5,000 to 13,000 bp containing ∼ 40 genes in total from the two ends of MPXV-79 were replaced with corresponding segments of USA-2003. Virulence was determined by live animal imaging in addition to weight loss and survival. Although there were statistical differences in survival and viral luminescence between the clade Ia and clade IIa MPXVs, no significant difference was found by replacing individual or multiple genes of clade Ia Z-79 with corresponding genes of clade IIa USA-2003. The absence of a significant reduction in virulence can have several explanations that would inform future experiments. |
| format | Article |
| id | doaj-art-cee30dca3f7546ec9f600402515a4b54 |
| institution | Kabale University |
| issn | 2222-1751 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-cee30dca3f7546ec9f600402515a4b542025-02-04T07:26:15ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2456144A functional approach to analyze the genetic basis for differences in virulence of monkeypox virus cladesPatricia L. Earl0Jeffrey L. Americo1Sara Reynolds2Wei Xiao3Catherine Cotter4Bernard Moss5Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USALaboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USALaboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USALaboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USALaboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USALaboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USAMpox, the disease caused by monkeypox virus (MPXV) is increasing in Africa and in 2022 spread to more than 100 countries sickening more than 100,000 individuals. Four clades of MPXV have been recognized with differences in severity of disease and extent of human-to-human transmission. Determination of the genetic basis for these differences could help to develop improved therapeutics and vaccines. The Castaneous (CAST) mouse is highly susceptible to MPXV and virulence differences of MPXV clades are statistically significant mimicking their relative severities in humans. The present study was intended to evaluate the CAST mouse as a model for investigating genomic differences by replacing genes of Zaire-1979 005 (Z-79) clade Ia MPXV with homologous gene sequences of the less virulent and less transmissible USA-2003 clade IIa MPXV. The expectation was that some gene replacements would reduce the virulence of Z-79 chimera. Recombinant viruses expressing firefly luciferase were constructed in which partially overlapping Z-79 DNA segments of 5,000 to 13,000 bp containing ∼ 40 genes in total from the two ends of MPXV-79 were replaced with corresponding segments of USA-2003. Virulence was determined by live animal imaging in addition to weight loss and survival. Although there were statistical differences in survival and viral luminescence between the clade Ia and clade IIa MPXVs, no significant difference was found by replacing individual or multiple genes of clade Ia Z-79 with corresponding genes of clade IIa USA-2003. The absence of a significant reduction in virulence can have several explanations that would inform future experiments.https://www.tandfonline.com/doi/10.1080/22221751.2025.2456144Mpoxmonkeypox virus cladesmonkeypox virus virulenceCastaneous mousechimeric viruses |
| spellingShingle | Patricia L. Earl Jeffrey L. Americo Sara Reynolds Wei Xiao Catherine Cotter Bernard Moss A functional approach to analyze the genetic basis for differences in virulence of monkeypox virus clades Emerging Microbes and Infections Mpox monkeypox virus clades monkeypox virus virulence Castaneous mouse chimeric viruses |
| title | A functional approach to analyze the genetic basis for differences in virulence of monkeypox virus clades |
| title_full | A functional approach to analyze the genetic basis for differences in virulence of monkeypox virus clades |
| title_fullStr | A functional approach to analyze the genetic basis for differences in virulence of monkeypox virus clades |
| title_full_unstemmed | A functional approach to analyze the genetic basis for differences in virulence of monkeypox virus clades |
| title_short | A functional approach to analyze the genetic basis for differences in virulence of monkeypox virus clades |
| title_sort | functional approach to analyze the genetic basis for differences in virulence of monkeypox virus clades |
| topic | Mpox monkeypox virus clades monkeypox virus virulence Castaneous mouse chimeric viruses |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2025.2456144 |
| work_keys_str_mv | AT patricialearl afunctionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT jeffreylamerico afunctionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT sarareynolds afunctionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT weixiao afunctionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT catherinecotter afunctionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT bernardmoss afunctionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT patricialearl functionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT jeffreylamerico functionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT sarareynolds functionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT weixiao functionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT catherinecotter functionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades AT bernardmoss functionalapproachtoanalyzethegeneticbasisfordifferencesinvirulenceofmonkeypoxvirusclades |