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Frequent detection of Saffold cardiovirus in adenoids.

ABSTRACT: Saffold virus (SAFV) is classified into the Cardiovirus genus of the Picornaviridae family. Up to now, eleven genotypes have been identified however, their clinical significance remains unclear. Here, we investigated the presence of SAFV in asymptomatic patients admitted for adenoidectomy. A total of 70 adenoid tissue samples were collected from children with clinical symptoms caused by hypertrophy of adenoids but without symptoms of airway infection. Samples were investigated for SAFV by RT-nested PCR and sequence analysis. Eleven of 70 (15.7%) samples were positive for SAFV. Nasopharyngeal swabs were available from 45 children just before surgery. SAFV was rarely found and only in children with SAFV-positive adenoids 2/8. Our findings indicate that the presence of SAFV seems to be more frequent in adenoid tissue than expected. This could support the notion of a longer than previously anticipated persistence of SAFV nucleic acids in the respiratory tract and possibly a chronic infection. Further investigations are necessary to establish the role of SAFV infection in humans.

SUBMITTER: Lindner K

PROVIDER: S-EPMC6608973 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Frequent detection of Saffold cardiovirus in adenoids.

Lindner Kira K Ludwig Michael M Bootz Friedrich F Reber Ulrike U Safavieh Zahrasadat Z Eis-Hübinger Anna Maria AM Herberhold Stephan S

PloS one 20190703 7

Saffold virus (SAFV) is classified into the Cardiovirus genus of the Picornaviridae family. Up to now, eleven genotypes have been identified however, their clinical significance remains unclear. Here, we investigated the presence of SAFV in asymptomatic patients admitted for adenoidectomy. A total of 70 adenoid tissue samples were collected from children with clinical symptoms caused by hypertrophy of adenoids but without symptoms of airway infection. Samples were investigated for SAFV by RT-nes ...[more]

PMID: 31269055

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Project description:In order to initiate an infection, viruses need to deliver their genomes into cells. This involves uncoating the genome and transporting it to the cytoplasm. The process of genome delivery is not well understood for nonenveloped viruses. We address this gap in our current knowledge by studying the uncoating of the nonenveloped human cardiovirus Saffold virus 3 (SAFV-3) of the family Picornaviridae SAFVs cause diseases ranging from gastrointestinal disorders to meningitis. We present a structure of a native SAFV-3 virion determined to 2.5 Å by X-ray crystallography and an 11-Å-resolution cryo-electron microscopy reconstruction of an "altered" particle that is primed for genome release. The altered particles are expanded relative to the native virus and contain pores in the capsid that might serve as channels for the release of VP4 subunits, N termini of VP1, and the RNA genome. Unlike in the related enteroviruses, pores in SAFV-3 are located roughly between the icosahedral 3- and 5-fold axes at an interface formed by two VP1 and one VP3 subunit. Furthermore, in native conditions many cardioviruses contain a disulfide bond formed by cysteines that are separated by just one residue. The disulfide bond is located in a surface loop of VP3. We determined the structure of the SAFV-3 virion in which the disulfide bonds are reduced. Disruption of the bond had minimal effect on the structure of the loop, but it increased the stability and decreased the infectivity of the virus. Therefore, compounds specifically disrupting or binding to the disulfide bond might limit SAFV infection.A capsid assembled from viral proteins protects the virus genome during transmission from one cell to another. However, when a virus enters a cell the virus genome has to be released from the capsid in order to initiate infection. This process is not well understood for nonenveloped viruses. We address this gap in our current knowledge by studying the genome release of Human Saffold virus 3 Saffold viruses cause diseases ranging from gastrointestinal disorders to meningitis. We show that before the genome is released, the Saffold virus 3 particle expands, and holes form in the previously compact capsid. These holes serve as channels for the release of the genome and small capsid proteins VP4 that in related enteroviruses facilitate subsequent transport of the virus genome into the cell cytoplasm.

Project description:The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3) isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months) and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible role in acute and/or chronic disease.

Dataset Information

Frequent detection of Saffold cardiovirus in adenoids.

Publications

Frequent detection of Saffold cardiovirus in adenoids.

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