Prevalence and genetic characteristics of Saffold cardiovirus in China from 2009 to 2012

Abstract

The epidemiology and clinical features of the Saffold cardiovirus (SAFV) remain ambiguous. The present study was designed to systematically and intensively investigate the epidemiological features of SAFV in pediatric patients in China. Three cohorts of pediatric patients were recruited from 2009 to 2012. Cohort 1 comprised patients with acute respiratory tract infections. Cohort 2 comprised patients with diarrhea. Cohort 3 comprised hand, foot, and mouth disease (HFMD) patients. A total of 115 patients (1.6%) among 6052 (17/1647, 12/2013, and 86/2392 in cohorts 1, 2, and 3, respectively) were SAFV-positive. The samples from 82 SAFV-positive patients were successfully sequenced, and four genotypes were identified: 8 SAFV-1, 41 SAFV-2, 29 SAFV-3, and 4 SAFV-6. A significantly higher detection rate was found in the HFMD patients than in other two cohorts (both P <0.001). A higher frequency of severe clinical outcome and nervous system manifestation were also observed in the SAFV-positive HFMD patients. Additionally, 6 (3.5%) cerebrospinal fluid and 7 (2.2%) serum samples from the HFMD-associated encephalitis patients were SAFV-positive. Based on the VP1 sequences, all four genotypes displayed distinct geographical clustering. SAFV infection might be associated with a wide clinical spectrum and contribute to HFMD.

Immunohistochemical insights into Saffold virus infection of the brain of juvenile AG129 mice

“…Phylogenetic analysis revealed that SAFV is closely related to Theiler’s murine encephalomyelitis virus (TMEV) [2, 3], a virus well studied for its neurovirulence [4]. Since then, SAFV have been isolated in children from multiple continents [1, 5–11] and have been shown to be highly prevalent in humans [7]. Recently, SAFV was found in the cerebrospinal fluid (CSF) of a previously healthy child that experienced sudden death [12], and in stool samples of children with non-polio acute flaccid paralysis [6], suggesting that the virus might be able to cause serious invasive infection of the central nervous system (CNS) of children [11].…”

“…Since then, SAFV have been isolated in children from multiple continents [1, 5–11] and have been shown to be highly prevalent in humans [7]. Recently, SAFV was found in the cerebrospinal fluid (CSF) of a previously healthy child that experienced sudden death [12], and in stool samples of children with non-polio acute flaccid paralysis [6], suggesting that the virus might be able to cause serious invasive infection of the central nervous system (CNS) of children [11]. TMEV, a virus similar to SAFV, is divided into two strains based on their neurovirulence after intracerebral inoculation [4]; the GDVII strain causes acute fatal poliomyelitis, killing all infected mice within 2 weeks, while DA strain causes milder encephalomyelitis, which then progresses to persistent infection and progressive demyelination reminiscent of multiple sclerosis [13].…”

“…Information about SAFV infection has increased in the past few years, with data concentrated on respiratory and gastrointestinal tract infections [11], however data informing CNS infection remains relatively low, despite its importance shown by clinical samples of SAFV found in children with neurological symptoms [6, 11, 12]. In this short paper, we examined SAFV infection of the brain in an animal model and presented important new insights to the neuropathogenesis of SAFV.…”

Saffold virus, an emerging human cardiovirus

“…Since then, SAFV has been isolated from nasal and stool specimens of children with respiratory and gastrointestinal symptoms in many countries . To date, 11 genotypes of SAFV have been identified on the basis of phylogenetic analysis of the VP1 gene with SAFV‐2 and SAFV‐3 having high seroprevalence …”

“…Initial work with SAFV was hindered by poor growth in laboratory cell lines . Subsequently, it was discovered that selected cell lines were indeed able to support the growth of SAFV (dependent on strain) thus the exponential increase in research data in recent years . These cell lines include Vero, HeLa, NIH/3 T3, CHO‐K1, Hep‐2, and Neuro2A .…”