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

• Published in: Viruses Vol. 8; no. 2; p. 24
• Main Authors: Tan, Shawn Zheng Kai, Chua, Kaw Bing, Xu, Yishi, Prabakaran, Mookkan
• Format: Journal Article
• Language: English
• 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
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v8020024

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.