Abstract
BackgroundSaffold cardiovirus (SAFV) is a new human cardiovirus with 11 identified genotypes. Little is known about the natural history and pathogenicity of SAFVs.Methodology/Principal FindingsWe sequenced the genome of five SAFV-1 strains which were identified from fecal samples taken from children with viral diarrhea in Beijing, China between March 2006 and November 2007, and analyzed the phylogenetic and phylodynamic properties of SAFVs using the genome sequences of every known SAFV genotypes. We identified multiple recombination events in our SAFV-1 strains, specifically recombination between SAFV-2, -3, -4, -9, -10 and the prototype SAFV-1 strain in the VP4 region and recombination between SAFV-4, -6, -8, -10, -11 and prototype SAFV-1 in the VP1/2A region. Notably, recombination in the structural gene VP4 is a rare event in Cardiovirus. The ratio of nonsynonymous substitutions to synonymous substitutions indicates a purifying selection of the SAFV genome. Phylogenetic and molecular clock analysis indicates the existence of at least two subclades of SAFV-1 with different origins. Subclade 1 includes two strains isolated from Pakistan, whereas subclade 2 includes the prototype strain and strains isolated in China, Pakistan, and Afghanistan. The most recent common ancestor of all SAFV genotypes dates to the 1710s, and SAFV-1, -2, and -3 to the 1940s, 1950s, and 1960s, respectively. No obvious relationship between variation and pathogenicity exists in the critical domains of the CD and EF loops of viral capsid proteins or the multi-functional proteins L based on animo acid sequence identity comparison between SAFV genotypes.Conclusions/SignificanceOur findings suggest that intertypic recombination plays an important role in the diversity of SAFVs, highlighting the diversity of the five strains with the previously described SAFV-1 strains.
Highlights
The newly identified Saffold cardiovirus (SAFV) is a member of the Cardiovirus genus and belongs to the Picornaviridae family [1]
We found that the five strains share nucleotide identities of 99.6–99.8% and amino acid identities of 99.3-99.7% between each other, and 88.9% and 97– 97.2% nucleotide and aa identities with the prototype SAFV genotype 1 (SAFV-1) strain (NC009448), respectively (Table 1)
Neither the SAFV-2 strains of the BR/118/2006 (EU681177), HTMV (NC010810), and UC6 (GU595289) isolates from Germany and the US nor the SAFV-3 stains of Pak3641 (AB747250), BCH1031 (GU943513), and NL1999 (HM181996) isolates from Pakistan, China, and the Netherlands appear to be involved in the recombination of the VP4 gene region. These findings suggest that our five SAFV-1 strains might derive from complicated recombination events between the prototype strain and multiple genotypes that circulate in nature
Summary
The newly identified Saffold cardiovirus (SAFV) is a member of the Cardiovirus genus and belongs to the Picornaviridae family [1]. SAFV is the member of the Theilovirus species, which includes Theiler’s murine encephalomyelitis virus (TMEV), Theiler-like rat virus (TRV), and Vilyuisk human encephalomyelitis virus (VHEV) [1,2,3]. The prototype strain of SAFV, designated as SAFV genotype 1 (SAFV-1), was identified in 2007 using genome sequencing [1]. It was first isolated in 1981, from a female child with fever of unknown origin in California, USA [1]. Saffold cardiovirus (SAFV) is a new human cardiovirus with 11 identified genotypes. Little is known about the natural history and pathogenicity of SAFVs
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