Saffold Virus, a Novel Human Cardiovirus with Unknown Pathogenicity

Abstract

Although cardioviruses have been thought to mainly infect rodents, a novel human cardiovirus, designated Saffold virus (SAFV), was identified in 2007. SAFV is grouped with Theiler-like rat virus and Theiler's murine encephalomyelitis virus (TMEV) in the species Theilovirus of the genus Cardiovirus of the family Picornaviridae. Eight genotypes of SAFV have now been identified. SAFV has been isolated from nasal and stool specimens from infants presenting with respiratory and gastrointestinal symptoms as well as from children with nonpolio acute flaccid paralysis; however, the relationship of SAFV to this symptomatology remains unclear. Of note, the virus has also been isolated from the cerebrospinal fluid specimens of patients with aseptic meningitis. This finding is of interest since TMEV is known to cause a multiple sclerosis-like syndrome in mice. The involvement of SAFV in various diseases (e.g., respiratory illness, gastrointestinal illness, neurological diseases, and type I diabetes) is presently under investigation. In order to clarify the pathogenicity of SAFV, additional epidemiological studies are required. Furthermore, identification of the SAFV cellular receptor will help establish an animal model for SAFV infection and help clarify the pathogenesis of SAFV-related diseases. In addition, investigation of the tissue-specific expression of the receptor may facilitate development of a novel picornavirus vector, which could be a useful tool in gene therapy for humans. The study of viral factors involved in viral pathogenicity using a reverse genetics technique will also be important.

The Crystal Structure of a Cardiovirus RNA-Dependent RNA Polymerase Reveals an Unusual Conformation of the Polymerase Active Site

“…All of these viruses infect rodents, replicate in the gastrointestinal tract, and are transmitted by the fecal-oral route. Although rodents are the natural reservoir of these viruses, EMCV has also been isolated from many other hosts, including various mammals, birds, and invertebrates (7,8). Infection of other mammalian species by EMCV is often fatal and associated with outbreaks of myocarditis and encephalitis.…”

Isolation of Saffold Virus Type 2 from Children with Acute Respiratory Infections by Using the RD-18S-Niigata Cell Line

“…Naeem et al recently characterized 11 genotypes, including 3 new genotypes, based on analysis of the complete virus protein (VP) 1 region (4-7). Among these 11 genotypes, SAFV types 2 and 3 (SAFV-2 and SAFV-3) are particularly common, causing widespread human viral infections in early childhood (2,3,(8)(9)(10). SAFVs have been detected in children presenting with respiratory tract infections, gastroenteritis, neurological diseases, and non-polio acute flaccid paralysis (2)(3)(4)(5)(6)(11)(12)(13)(14).…”

“…Among these 11 genotypes, SAFV types 2 and 3 (SAFV-2 and SAFV-3) are particularly common, causing widespread human viral infections in early childhood (2,3,(8)(9)(10). SAFVs have been detected in children presenting with respiratory tract infections, gastroenteritis, neurological diseases, and non-polio acute flaccid paralysis (2)(3)(4)(5)(6)(11)(12)(13)(14). However, the epidemiological characteristics, distribution, prevalence, diversity, disease spectrum, and pathogenic role of SAFVs are still not fully understood; indeed, the description of SAFVs in the latest pediatrics textbook published in 2014 runs to only a few lines (2,3,15,16).…”

“…When no CPE was observed, we transferred the inoculated culture fluid onto a freshly prepared plate until the 4th passage. Eagle's minimum essential medium 1) 1,000 ml Fetal bovine serum 2) 80 ml 7.5z sodium bicarbonate 4) 15 ml Fangizon 6) 5 ml Gentamicin 2) 5 ml L-glutamine 4) 10 ml…”

Role(s) of Leader protein of Saffold virus

“…[1][2][3][4][5][6] Although several epidemiological studies have been reported, the precise relationship between SAFV and human diseases still remains unclear. 7 Theiler's original (TO) subgroup strains (Daniel's strain [DA] is the representative strain) of TMEV cause a milder polioencephalomyelitis followed by virus persistence and demyelination in the spinal cords of mice. The demyelination induced by TO subgroup strains is the representative of virus-induced demyelination and serves as an excellent animal model for multiple sclerosis (MS), as its pathological features are reminiscent of MS. 8 Viruses in the genus Cardiovirus contain Leader protein (L) coding region at the most 5 0 -terminus of the open reading frame.…”