title: The Pathogenesis of Saffold Virus in AG129 Mice and the Effects of Its Truncated L Protein in the Central Nervous System.
abstract: Saffold Virus (SAFV) is a human cardiovirus that has been suggested to cause severe infection of the central nervous system (CNS). Compared to a similar virus, Theiler's murine encephalomyelitis virus (TMEV), SAFV has a truncated Leader (L) protein, a protein essential in the establishment of persistent CNS infections. In this study, we generated a chimeric SAFV by replacing the L protein of SAFV with that of TMEV. We then compared the replication in cell cultures and pathogenesis in a mouse model. We showed that both SAFV and chimeric SAFV are able to infect Vero and Neuro2a cells well, but only chimeric SAFV was able to infect RAW264.7. We then showed that mice lacking IFN-α/β and IFN-γ receptors provide a good animal model for SAFV infection, and further identified the locality of the infection to the ventral horn of the spine and several locations in the brain. Lastly, we showed that neither SAFV nor chimeric SAFV causes persistence in this model. Overall, our results provide a strong basis on which the mechanisms underlying Saffold virus induced neuropathogenesis can be further studied and, hence, facilitating new information about its pathogenesis.
authors.affiliation: Temasek Life Science Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore. shawntanzk@tll.org.sg.
authors.forename: Shawn Zheng Kai
authors.initials: SZ
authors.lastname: Tan
authors.affiliation: Temasek Life Science Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore. chuakb@tll.org.sg.
authors.forename: Kaw Bing
authors.initials: KB
authors.lastname: Chua
authors.affiliation: Temasek Life Science Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore. yishi@tll.org.sg.
authors.forename: Yishi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Temasek Life Science Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore. prabakar@tll.org.sg.
authors.forename: Mookkan
authors.initials: M
authors.lastname: Prabakaran
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D017943:Cardiovirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D018188:Cardiovirus Infections / Q000473:pathology / Q000821:virology*; D002490:Central Nervous System / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D016679:Genome, Viral; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014774:Virulence; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins
keywords: L protein; Saffold virus; central nervous system