Role(s) of Leader protein of Saffold virus

Abstract

Objective Saffold virus (SAFV) classified in the species Theilovirus of the genus Cardiovirus is a novel human cardiovirus. The pathogenicity of SAFV in humans still remains unclear. Viruses in the genus Cardiovirus produce Leader protein, which is a small non-structural protein. Evidence that Leader protein of murine cardioviruses is a key factor in their biological activities has been provided. Therefore, the studies on the function of SAFV-L are likely to be important in order to clarify the pathogenicity of SAFV. Methods We investigated the interferon (IFN) response in the early stage of SAFV infection by reverse transcription polymerase chain reaction and the growth kinetics of the chimera virus, SAFL/DA. Results The study showed that SAFV-L suppresses the type I IFN response, and that the responsible region of anti-IFN activity of SAFV-L is a zincbinding motif. Furthermore, the anti-apoptotic activity of SAFV-L was suggested from the growth kinetics analysis of SAFL/DA. Conclusions The present study suggested that SAFV-L might be a multifunctional protein; for example, the suppression of IFN induction, antiapoptotic effect and/or productive virus growth.

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

“…When analyzed, the homology of L between SAFV and TMEV DA strains is 78%. While a chimeric SAFV containing TMEV L protein has been previously developed and studied [ 15 ], the authors only explored its role in suppression of interferon, while the functional impact and difference in specific biological activities caused by this difference is still relatively unknown.…”

Paeoniflorin suppresses vascular damage and the expression of E‐selectin and ICAM‐1 in a mouse model of cutaneous Arthus reaction

“…30 ll in PBS) into the left ear followed immediately by i.v. injection of chicken ovalbumin 200 lg, as previously reported (1)(2)(3). Unless otherwise stated, the intradermal injection of non-immunizing rabbit IgG (40 lg/30 ll in PBS) followed by intravenous introduction of chicken egg albumin 200 lg served as a control.…”

“…Cutaneous reverse passive Arthus (RPA) reaction is a classical and important animal model of CV, in which IC-induced endothelial inflammatory responses play essential roles. Hence, there is an increasing interest to explore and develop novel therapeutic strategies to interfere with vascular damage, and perivascular leucocyte infiltrates in IC-induced Arthus reaction (2)(3)(4).…”

Saffold virus, an emerging human cardiovirus

“…However, they were unable to rescue the recombinant viruses, even after 3 blind passages. Similarly, Shimizu et al generated chimeric SAFV and TMEV by replacing L protein of SAFV with that of TMEV DA strain and vice versa and studied their effects on interferons. Very recently, our laboratory generated an infectious cDNA clone of SAFV under the control of a human RNA polymerase 1 (hpol1) promoter (Figure B) .…”

“…It also eliminates the need to add extra bases during in vivo transcription at the 5’ and 3’ ends of viral transcripts . Overall, studies using chimeric SAFV containing TMEV L have shown that the L protein is at least partially responsible for differences in suppression of interferons, cell tropism, pathogenicity of the virus, and nucleocytoplasmic trafficking …”