title: Pathogenesis of fulminant monkeypox with bacterial sepsis after experimental infection with West African monkeypox virus in a cynomolgus monkey.
abstract: The pathogenesis of severe human monkeypox, which causes systemic and fulminant infections, is not clear. This study presents a case repot of fulminant monkeypox with bacterial sepsis after experimental infection with monkeypox virus in a cynomolgus monkey (Macaca fascicularis). In our previous study (Saijo et al., 2009, J Gen Virol), two cynomolgus monkeys became moribund after experimental infection with monkeypox virus Liberia strain, West African strain. One exhibited typical monkeypox-related papulovesicular lesions. The other monkey presented fulminant clinical symptoms with a characteristic flat red rash similar to that found in smallpox, which is associated with extremely high fatality rates. In this study, we found that the monkey with flat red rash had high levels of viremia and neutropenia, as well as high plasma levels of pro-inflammatory cytokines and chemokines compared with the other monkey. Monkeypox virus replicates in epithelial cells and macrophages in various organs. Sepsis due to Gram-positive cocci was confirmed histopathologically in the monkey with flat red rash. The lack of inflammatory response in the lesion suggested that the monkey with sepsis experienced strong immune suppression during the viral infection. The neutropenia and excessive inflammatory cytokine responses indicate that neutrophils play key roles in the pathogenesis of systemic and fulminant human monkeypox virus infections with sepsis.
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saijo
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Kataoka
authors.affiliation: Department of Division of Experimental Animals Research, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ami
authors.affiliation: Department of Division of Experimental Animals Research, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Suzaki
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwata-Yoshikawa
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Ogata
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurane
authors.affiliation: Department of Veterinary Science, National Institute of Infectious Diseases 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morikawa
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016908:Gram-Positive Bacterial Infections / Q000150:complications* / Q000276:immunology; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D045908:Mpox, Monkeypox / Q000276:immunology* / Q000473:pathology* / Q000662:veterinary*; D008993:Monkeypox virus / Q000472:pathogenicity; D009503:Neutropenia / Q000276:immunology / Q000662:veterinary / Q000821:virology; D018805:Sepsis / Q000150:complications* / Q000276:immunology
keywords: Animal model; cynomolgus monkey; cytokine; monkeypox; neutropenia