20 Oct 2022
DOI: 10.1126/science.add4153
CRYSTAL M. GIGANTE , BETTE KORBER, MATTHEW H. SEABOLT, KIMBERLY WILKINS, WHITNI DAVIDSON, AGAM K. RAO, HUI ZHAO, TODD G. SMITH, CHRISTINE M. HUGHES , FAISAL MINHAJ , MICHELLE A. WALTENBURG, JAMES THEILER, SANDRA SMOLE , GLEN R. GALLAGHER, DAVID BLYTHE, ROBERT MYERS, JOANN SCHULTE, JOEY STRINGER, PHILIP LEE, RAFAEL M. MENDOZA, LATOYA A. GRIFFIN-THOMAS, JENNY CRAIN , JADE MURRAY, ANNETTE ATKINSON, ANTHONY H. GONZALEZ, JUNE NASH, DHWANI BATRA , INGER DAMON, JENNIFER MCQUISTON, CHRISTINA L. HUTSON, ANDREA M. MCCOLLUM , AND YU LI
Abstract
Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of monkeypox virus (MPXV) among two 2021 and seven 2022 U.S. monkeypox cases: the major 2022 outbreak variant, B.1, and a minor contemporaneously sampled variant called A.2. Analyses of mutations among these two variants revealed an extreme preference for GA-to-AA mutations indicative of human APOBEC3 cytosine deaminase activity among Clade IIb MPXV (previously West African, Nigeria) sampled since 2017. Such mutations were not enriched within other MPXV clades. These findings suggest that APOBEC3 editing may be a recurrent and a dominant driver of MPXV evolution within the current outbreak.