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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:CMI Communications
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Online Access:http://www.sciencedirect.com/science/article/pii/S295059092405042X
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Summary: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.
ISSN:2950-5909