Genomic characterization of the recent monkeypox outbreak

Abstract

The Monkeypox virus is the etiological cause of a recent multi-country outbreak, with nearly one hundred distinct cases detected outside the endemic areas of Africa in May 2022. In this article, we analyze the sequences of two full genomes of Monkeypox virus from Portugal and Belgium, and compare them with all available Monkeypox sequences, annotated by year and geographic origin, as well as related Cowpox and Variola (smallpox) virus sequences. Our results show that the recent outbreak is most likely originating from the West African clade of Monkeypox, with >99% sequence identity with sequences derived from historical and recent cases, dating from 1971 to 2017. We analyze specific mutations occurring in viral proteins A42R (for which a crystal structure is available) and H3L (an important epitope in host immune recognition), highlighting specific amino acids varying between the current outbreak, previous Monkeypox and Cowpox sequences and the historical Variola virus. Genome-wide sequence analysis of the recent outbreak and other monkeypox/cowpox/variola viruses shows a very high conservation, with 97.9% (protein-based) and 97.8% (nucleotide-based) sequence identity.