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Virulence differences between monkeypox virus isolates from West Africa and the Congo basin
Authors:Chen Nanhai  Li Guiyun  Liszewski M Kathryn  Atkinson John P  Jahrling Peter B  Feng Zehua  Schriewer Jill  Buck Charles  Wang Chunlin  Lefkowitz Elliot J  Esposito Joseph J  Harms Tiara  Damon Inger K  Roper Rachel L  Upton Chris  Buller R Mark L
Affiliation:a Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, M432, 1402 South Grand Boulevard, St. Louis, MO 63104, USA
b Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada V8W 2Y2
c Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
d Headquarters, United States Army Research Institute of Infectious Diseases, Frederick, MD 21702, USA
e Virology Collection, ATCC, Manassas, VA 20108, USA
f Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
g National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
h Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
Abstract:Studies indicate that West African and Congo basin isolates of monkeypox virus (MPXV) are genetically distinct. Here, we show Congo basin MPXV-ZAI-V79 is more virulent for cynomolgus monkeys as compared to presumed West African MPXV-COP-58. This finding may explain the lack of case-fatalities in the U.S. 2003 monkeypox outbreak, which was caused by a West African virus. Virulence differences between West African and Congo basin MPXV are further supported by epidemiological analyses that observed a similar prevalence of antibodies in non-vaccinated humans in both regions, while >90% of reported cases occurred in the Congo basin, and no fatal cases were observed outside of this region. To determine the basis for this difference in virulence, we sequenced the genomes of one human West African isolate, and two presumed West African isolates and compared the sequences to Congo basin MPXV-ZAI-96-I-16. The analysis identified D10L, D14L, B10R, B14R, and B19R as possible virulence genes, with D14L (ortholog of vaccinia complement protein) as a leading candidate.
Keywords:Monkeypox   Genomic sequences   Genetic diversity   Virulence genes   Non-human primates
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