Monkeypox virus 2022, gene heterogeneity and protein polymorphism

Abstract Human monkeypox (MPX) had been confined to equatorial Africa as an endemic disease1,2. Since early May 2022, cases of human MPX have been explosively reported from countries where the disease is not endemic. This is the first time that many human cases have been reported concurrently in non-endemic and endemic countries in widely disparate geographical areas3,4. Here we analyze 27 genes or sequences from 643 full-length genomes of human monkeypox viruses (MPXVs) established after January 1, 2022. These MPXVs can converge into one branch on the phylogenetic trees of E3L, B13R, B19R, C7L, D11L, N1R, T4, and K4L genes, but can be divided into two, two-plus, or irregular branches on the phylogenetic trees of other genes or sequences. Due to the early appearance of the stop codons, the proteins encoded by D7L, O1L, B5R, B14R, and T4 genes of MPXVs 2022 can be truncated into different lengths, showing polymorphism in length. In particular, MPXVs 2022 had acquired or retained at least two virulent genes (B14R and T4) that do not belong to the ancient West African clade strains. Heterogeneity of genes and polymorphism of proteins may reflect the viruses’ complex epidemic history and the impacts they may suffer from environments, hosts and vectors. These impacts in turn prompt the viruses to frequently acquire, lose, truncate and delete genes. The acquisition or retain virulent genes with functional products of B14R and T4 may affect the virulence and the capacity of human-to-human transmission of MPXVs 2022, and may be responsible for their unprecedented expansions in infected population and epidemic areas.