AUTHOR=Diaz-Cánova Diana , Moens Ugo L. , Brinkmann Annika , Nitsche Andreas , Okeke Malachy Ifeanyi TITLE=Genomic Sequencing and Analysis of a Novel Human Cowpox Virus With Mosaic Sequences From North America and Old World Orthopoxvirus JOURNAL=Frontiers in Microbiology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.868887 DOI=10.3389/fmicb.2022.868887 ISSN=1664-302X ABSTRACT=Orthopoxviruses (OPXV) not only infect their natural hosts but can also cause disease in humans. Previously, we partially characterized an orthopoxvirus isolated from an 18-year-old male living in Northern Norway. Electron microscopy studies and partial genome sequencing characterized this virus as an atypical cowpox virus, which we named CPXV-No-H2. In this study, we determined the complete genome sequence of CPXV-No-H2 using Illumina and Nanopore sequencing. Our results showed that the whole CPXV-No-H2 genome is 220,276 base-pairs (bp) long with inverted terminal repeats regions of approximately 7 kbp, containing 217 predicted genes. Seventeen predicted CPXV-No-H2 proteins were most similar to OPXV proteins from the Old World, including Ectromelia virus and Vaccinia virus, and the North America, Alaskapox virus. CPXV-No-H2 has a mosaic genome with genes most similar to other OPXV genes and seven potential recombination events were identified. Phylogenetic analysis showed that CPXV-No-H2 formed a separate clade with the German CPXV isolates CPXV_GerMygEK938_17 and CPXV_Ger2010_MKY, sharing 96.4% and 96.3% nucleotide identity, respectively and this clade clustered closely with the ECTV-OPXV Abatino clade. CPXV-No-H2 is a mosaic virus that may have arisen out of several recombination events between OPXV and its phylogenetic clustering suggests that ECTV-Abatino-like cowpox viruses form a distinct, new clade of cowpox viruses.