The Pathogenesis of Saffold Virus in AG129 Mice and the Effects of Its Truncated L Protein in the Central Nervous System

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 p...

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Published inViruses Vol. 8; no. 2; p. 24
Main Authors Tan, Shawn Zheng Kai, Chua, Kaw Bing, Xu, Yishi, Prabakaran, Mookkan
Format Journal Article
LanguageEnglish
Published Switzerland MDPI 18.02.2016
MDPI AG
Subjects
Animals
Capsid Proteins - genetics
Capsid Proteins - metabolism
Cardiovirus - genetics
Cardiovirus - pathogenicity
Cardiovirus - physiology
Cardiovirus Infections - pathology
Cardiovirus Infections - virology
central nervous system
Central Nervous System - pathology
Central Nervous System - virology
Disease Models, Animal
Female
Genome, Viral
Humans
L protein
Mice
Mice, Inbred BALB C
Saffold virus
Virulence
Virus Replication
L protein
Saffold virus
central nervous system
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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.
AbstractList 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.
Author Prabakaran, Mookkan
Chua, Kaw Bing
Xu, Yishi
Tan, Shawn Zheng Kai
AuthorAffiliation Temasek Life Science Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore; shawntanzk@tll.org.sg (S.Z.K.T.); chuakb@tll.org.sg (K.B.C.); yishi@tll.org.sg (Y.X.)
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crossref_primary_10_3389_fimmu_2023_1194842
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Keywords L protein
Saffold virus
central nervous system
Language English
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Snippet 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,...
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SubjectTerms Animals
Capsid Proteins - genetics
Capsid Proteins - metabolism
Cardiovirus - genetics
Cardiovirus - pathogenicity
Cardiovirus - physiology
Cardiovirus Infections - pathology
Cardiovirus Infections - virology
central nervous system
Central Nervous System - pathology
Central Nervous System - virology
Disease Models, Animal
Female
Genome, Viral
Humans
L protein
Mice
Mice, Inbred BALB C
Saffold virus
Virulence
Virus Replication
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Title The Pathogenesis of Saffold Virus in AG129 Mice and the Effects of Its Truncated L Protein in the Central Nervous System
URI https://www.ncbi.nlm.nih.gov/pubmed/26901216
https://search.proquest.com/docview/1767916106
https://pubmed.ncbi.nlm.nih.gov/PMC4776182
https://doaj.org/article/c35aefe189a64fcd82a0747ec264c259
Volume 8
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