Genetic variability, including gene duplication and deletion, in early sequences from the 2022 European monkeypox outbreak

Abstract

Genome sequences from 47 monkeypox virus infections detected in a German university virology laboratory were analyzed in context of other sequences from the 2022 outbreak and earlier monkeypox genomes. Identical non-synonymous amino acid changes in six genes and the signature of APOBEC editing match other sequences from the European outbreak. Non-synonymous changes that were present in one to three sequences were found in 34 other genes. In sequences from two lesions of one patient, an 856 nucleotide translocation between genome termini resulted in the duplication of an initial (5-prime end) gene, and the disruption or complete deletion of four genes near the (3-prime) genome end. Orthopoxvirus genome rearrangements of this nature are known to confer fitness advantages in the face of selection pressure. This change may therefore represent an early virus adaptation in the novel widespread and sustained human-to-human context of the current monkeypox outbreak.

Sequencing of Monkeypox virus from infected patients reveals viral genomes with APOBEC3-like editing, gene inactivation, and bacterial agents of skin superinfection

“…The impact of these mutations on the function of these proteins and on the viral replication cycle is worthy to be investigated. Interestingly, we observed, as previously reported by other teams (Isidro et al, 2022b; Wang et al, 2022; Jones et al, 2022; Otoole and Rambaut, 2022), that three amino acid changes implicated the B21 protein (OPG210 gene in the genome NC_063383.1), a surface putative membrane-associated glycoprotein similar to Vaccinia virus VACV-WR B21R protein. This protein has been found to be highly immunogenic (Hammarlund et al, 2005), and this questions if these amino acid changes may have been selected as they might lead to viral immune escape.…”

“…Another interesting observation is the high number of mutations (between 66 and 73) in MPX virus genomes obtained here compared to the NC_063383.1 genome obtained from a human specimen collected in Nigeria in August 2018, which is in the same range than previously reported (Isidro et al, 2022b; Wang et al, 2022; Jones et al, 2022; Otoole and Rambaut, 2022). This corresponds to a greater mutation rate than that expected based on previous assessment for orthopoxviruses that was estimated to be 1–2 nucleotide substitutions per genome per year (i.e.…”

“…The analysis of the 18 MPX virus genomes obtained in the present study showed the presence of non-synonymous mutations leading to amino acid changes in dozens of viral proteins involved in virion replication and morphogenesis, as well as in virus-host interactions, including some that are deemed to be central for the viral cycle. Such mutations have been detected in several other European studies (Isidro et al, 2022b; Wang et al, 2022; Jones et al, 2022; Otoole and Rambaut, 2022). Proteins affected by amino acid changes include for instance DNA and RNA polymerase subunits; transcription or elongation factors; virion core proteins; the major envelope protein; a putative membrane-associated glycoprotein; ankyrin-repeat containing proteins; and a phospholipase D-like protein.…”

“…The B.1 lineage has been estimated to have emerged in Europe on early February 2022, most probably between November 2021 and May 2022 (Luna et al, 2022). Interestingly, the MPX viruses that cause the 2022 outbreak were found to diverge from those of the A.1 lineage by approximately 50 nucleotide substitutions (Isidro et al, 2022b; Wang et al, 2022; Jones et al, 2022), which is roughly 10 times more than expected on the basis of previous estimates of the orthopoxvirus mutation rate of 1–2 substitutions per genome per year (Firth et al, 2010).…”

“…In France, the first draft genome was released on 25/05/2022 in Southwest France (Croville et al, 2022). Phylogenomic studies of MPX viruses involved in this 2022 outbreak indicated that these viruses belong to clade 3 and likely have a single origin (Isidro et al, 2022b; Wang et al, 2022; Jones et al, 2022). They further indicated that these viruses comprise a lineage named B.1 that derives from the A.1 lineage whose members were associated with the large outbreak in 2017-2018 in Nigeria and with MPX virus exportation from Nigeria to the United Kingdom, Israel and Singapore in 2018-2019 (Mauldin et al, 2022; Isidro et al, 2022b).…”