Genetic variability of mpox sequences
A total of 162 sequences (SRA, BioProject: PRJNA944928) were produced from 148 patients (some patients had two samples). Among them, 32 different mutational patterns were distinguished – defined in comparison to the ON602722.2 reference sequence. Pattern #1 was identical to ON602722.2, while patterns #2 to #32 harbored at least one mutation (Supplementary Table S2 ). Pattern #1 included most of the sequences (n=120, 74.1%), and pattern #9 encompassed 10 sequences (6.2%). All other mutational patterns included only one or two sequences. Fourteen patterns were already reported in the GenBank database. The most common ones are patterns #9 and 13 observed in 6.16% and 1% of the GenBank sequences, respectively (Supplementary Table S2 ). Others were observed in less than 1% of GenBank sequences. Interestingly, all of the sequences produced in this study included a 17-nucleotide deletion (position 150,621, intergenic). This deletion was a succession of 17-nucleotides repeated sequence and was present in only 30% of the 5,661 GenBank mpox sequences (15th March 2023), and 32% of 5,306 described during the 2022 outbreak. One sequence included an unreported 4 nt-deletion, pattern #8. One sequence included an unreported 4 nt-deletion (position 14,509, ORF OPG25). Overall, 51% of mutations were non-synonymous, 37% synonymous, and 12% non-coding. A majority of transitions (17 G-to-A; 17 C-to-T) was observed, confirming a highly specific mutational typology.
Of note, a comparison of pre-epidemic strain MT903344.1 and the French MPXV_FRA_2022_TLS67 outbreak strain (ON602722.2) identified more mutations (58 substitutions and 27 indels along the genome) (Supplementary Table S3 ).