title: Experimental evaluation of the zoonotic infection potency of simian retrovirus type 4 using humanized mouse model.
abstract: During 2001-2002 and 2008-2011, two epidemic outbreaks of infectious hemorrhagic disease have been found in Japanese macaques (Macaca fuscata) in Kyoto University Primate Research Institute, Japan. Following investigations revealed that the causative agent was simian retrovirus type 4 (SRV-4). SRV-4 was isolated by using human cell lines, which indicates that human cells are potently susceptible to SRV-4 infection. These raise a possibility of zoonotic infection of pathogenic SRV-4 from Japanese macaques into humans. To explore the possibility of zoonotic infection of SRV-4 to humans, here we use a human hematopoietic stem cell-transplanted humanized mouse model. Eight out of the twelve SRV-4-inoculated humanized mice were infected with SRV-4. Importantly, 3 out of the 8 infected mice exhibited anemia and hemophagocytosis, and an infected mouse died. To address the possibility that SRV-4 adapts humanized mouse and acquires higher pathogenicity, the virus was isolated from an infected mice exhibited severe anemia was further inoculated into another 6 humanized mice. However, no infected mice exhibited any illness. Taken together, our findings demonstrate that the zoonotic SRV-4 infection from Japanese macaques to humans is technically possible under experimental condition. However, such zoonotic infection may not occur in the real society.
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.|CREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sato
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Misawa
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.|Laboratory of Signal Transduction, Institute for Virus Research, Kyoto University, Kyoto, Japan.|Laboratory of Virolution, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Rokusuke
authors.initials: R
authors.lastname: Yoshikawa
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Junko S
authors.initials: JS
authors.lastname: Takeuchi
authors.affiliation: Laboratory of Primate Model, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
authors.affiliation: Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Jun-ichirou
authors.initials: J
authors.lastname: Yasunaga
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.affiliation: Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
authors.affiliation: Laboratory of Signal Transduction, Institute for Virus Research, Kyoto University, Kyoto, Japan.|Laboratory of Virolution, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miyazawa
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
mesh_terms: D000071478:APOBEC Deaminases; D000818:Animals; D002460:Cell Line; D003564:Cytidine Deaminase; D016207:Cytokines / Q000378:metabolism; D043525:Cytosine Deaminase / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D006801:Humans; D007564:Japan; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D023421:Models, Animal; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D012192:Retroviridae Infections / Q000473:pathology / Q000635:transmission* / Q000821:virology; D015301:Retroviruses, Simian / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D014183:Transplantation, Heterologous; D015047:Zoonoses / Q000635:transmission* / Q000821:virology
chemical_list: D016207:Cytokines; D012367:RNA, Viral; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase