Multiple-clone infections of Mpox: Insights from a single primary lesion
Objectives: The 2022 Mpox epidemic transitioned to human-to-human transmission through primary lesions, showing a higher rate of genomic mutations than typical for a DNA virus. While Orthopoxviruses are traditionally considered to cause monoclonal infections in a single patient, we explored whether...
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Elsevier
2024-12-01
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| Series: | CMI Communications |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S295059092405042X |
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| author | Natsuko Kaku Mayo Yasugi Evariste Tshibangu-Kabamba Yoshiyuki Wakabayashi Yuko Uesaka Yu Nakagama Takuto Nogimori Takuya Yamamoto Placide Mbala-Kingebeni Dieudonné Mumba Ngoyi Eisuke Adachi Yasutoshi Kido |
| author_facet | Natsuko Kaku Mayo Yasugi Evariste Tshibangu-Kabamba Yoshiyuki Wakabayashi Yuko Uesaka Yu Nakagama Takuto Nogimori Takuya Yamamoto Placide Mbala-Kingebeni Dieudonné Mumba Ngoyi Eisuke Adachi Yasutoshi Kido |
| author_sort | Natsuko Kaku |
| collection | DOAJ |
| description | Objectives: The 2022 Mpox epidemic transitioned to human-to-human transmission through primary lesions, showing a higher rate of genomic mutations than typical for a DNA virus. While Orthopoxviruses are traditionally considered to cause monoclonal infections in a single patient, we explored whether Mpox virus (MPXV) exhibits genomic plasticity in primary lesions. Methods: Five clones, A3, A4, B3, C2, and C5, were isolated from a primary skin lesion of an adult male patient with Mpox and human immunodeficiency virus on antiretroviral therapy, who was not immunocompromised. Whole-genome sequencing was performed to analyze single nucleotide variations in each clone. The tissue culture infectious dose 50 (TCID50) and cytopathic effects (CPE) were measured at one, three, and six days post-infection as in vitro virus phenotypes. Results: Clones A4, C2, and C5 had dominantly identical sequences, while minor clones A3 and B3 had probably three and certainly one additional unique mutation, respectively. Four mutations in A3 and B3 were located in the viral open reading frames, with A3 causing amino acid substitutions at two sites in B21R and B3 resulting in one amino acid change in I6L. Although there were no significant differences in TCID50 levels among the clones, B3 showed a greater CPE than the others at three and six days post-infection. Conclusions: The coexistence of multiple clones with distinct genotypes and viral characteristics within a primary lesion suggests genomic plasticity in MPXV, indicating that genomic diversity may arise early in infection. |
| format | Article |
| id | doaj-art-b7b60184e6d34bd296ca6f02ed8923b2 |
| institution | Kabale University |
| issn | 2950-5909 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | CMI Communications |
| spelling | doaj-art-b7b60184e6d34bd296ca6f02ed8923b22025-08-20T03:42:45ZengElsevierCMI Communications2950-59092024-12-011310504210.1016/j.cmicom.2024.105042Multiple-clone infections of Mpox: Insights from a single primary lesionNatsuko Kaku0Mayo Yasugi1Evariste Tshibangu-Kabamba2Yoshiyuki Wakabayashi3Yuko Uesaka4Yu Nakagama5Takuto Nogimori6Takuya Yamamoto7Placide Mbala-Kingebeni8Dieudonné Mumba Ngoyi9Eisuke Adachi10Yasutoshi Kido11Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, Japan; Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, JapanGraduate School of Veterinary Science, Osaka Metropolitan University, 1-58 Rinkuoraikita, Izumisano, Osaka 598-0048, Japan; Asian Health Science Research Institute, Osaka Metropolitan University, 1-58 Rinkuoraikita, Izumisano, Osaka 598-0048, JapanGraduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, Japan; Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, Japan; University of Mbujimayi, VJWG+4H7, Avenue Lumumba, Mbuji-Mayi, Democratic Republic of the CongoGraduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, Japan; Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, JapanGraduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, Japan; Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, JapanGraduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, Japan; Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, JapanCenter for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085, JapanCenter for Intractable Diseases and ImmunoGenomics, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085, JapanInstitut National de Recherche Biomédicale, Ministère de la Santé Publique, M8R2+4WX, Kinshasa, Democratic Republic of the CongoInstitut National de Recherche Biomédicale, Ministère de la Santé Publique, M8R2+4WX, Kinshasa, Democratic Republic of the CongoIMSUT Hospital of The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato City, Tokyo 108-8639, JapanGraduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, Japan; Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, Japan; Corresponding author at: Department of Virology and Parasitology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahimachi, Abeno Ward, Osaka 545-8585, Japan.Objectives: The 2022 Mpox epidemic transitioned to human-to-human transmission through primary lesions, showing a higher rate of genomic mutations than typical for a DNA virus. While Orthopoxviruses are traditionally considered to cause monoclonal infections in a single patient, we explored whether Mpox virus (MPXV) exhibits genomic plasticity in primary lesions. Methods: Five clones, A3, A4, B3, C2, and C5, were isolated from a primary skin lesion of an adult male patient with Mpox and human immunodeficiency virus on antiretroviral therapy, who was not immunocompromised. Whole-genome sequencing was performed to analyze single nucleotide variations in each clone. The tissue culture infectious dose 50 (TCID50) and cytopathic effects (CPE) were measured at one, three, and six days post-infection as in vitro virus phenotypes. Results: Clones A4, C2, and C5 had dominantly identical sequences, while minor clones A3 and B3 had probably three and certainly one additional unique mutation, respectively. Four mutations in A3 and B3 were located in the viral open reading frames, with A3 causing amino acid substitutions at two sites in B21R and B3 resulting in one amino acid change in I6L. Although there were no significant differences in TCID50 levels among the clones, B3 showed a greater CPE than the others at three and six days post-infection. Conclusions: The coexistence of multiple clones with distinct genotypes and viral characteristics within a primary lesion suggests genomic plasticity in MPXV, indicating that genomic diversity may arise early in infection.http://www.sciencedirect.com/science/article/pii/S295059092405042XMpox virusMultiple-clone infectionsGenomic plasticityIntra-host evolutionHuman-to-human transmission |
| spellingShingle | Natsuko Kaku Mayo Yasugi Evariste Tshibangu-Kabamba Yoshiyuki Wakabayashi Yuko Uesaka Yu Nakagama Takuto Nogimori Takuya Yamamoto Placide Mbala-Kingebeni Dieudonné Mumba Ngoyi Eisuke Adachi Yasutoshi Kido Multiple-clone infections of Mpox: Insights from a single primary lesion CMI Communications Mpox virus Multiple-clone infections Genomic plasticity Intra-host evolution Human-to-human transmission |
| title | Multiple-clone infections of Mpox: Insights from a single primary lesion |
| title_full | Multiple-clone infections of Mpox: Insights from a single primary lesion |
| title_fullStr | Multiple-clone infections of Mpox: Insights from a single primary lesion |
| title_full_unstemmed | Multiple-clone infections of Mpox: Insights from a single primary lesion |
| title_short | Multiple-clone infections of Mpox: Insights from a single primary lesion |
| title_sort | multiple clone infections of mpox insights from a single primary lesion |
| topic | Mpox virus Multiple-clone infections Genomic plasticity Intra-host evolution Human-to-human transmission |
| url | http://www.sciencedirect.com/science/article/pii/S295059092405042X |
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