Intertypic recombination of human parechovirus 4 isolated from infants with sepsis-like disease
Section snippets
Background
Human parechoviruses (HPeVs) are non-enveloped, single-stranded, positive-sense RNA-viruses and members of the family Picornaviridae. The HPeV genome, approximately 7350 nucleotides (nt) in size, encodes for a single polyprotein, which consists of three regions: P1, P2 and P3. The polyprotein is cleaved post-translationally into three structural (VP0, VP3 and VP1 from P1) and seven non-structural proteins (2A, 2B, 2C from P2 and 3A-3D from P3) [1]. Both ends of the coding sequence (CDS) are
Objectives
Three HPeV-4 isolates from different infants were isolated during autumn 2012, sequenced and their complete coding sequences were analyzed for sequence similarity and recombination events. These HPeV–4 s were the first type 4 HPeVs found in Finland, and caused a small outbreak of sepsis-like disease in infants. Sepsis-like disease is a more common clinical outcome for HPeV-3, so these viruses caused more severe symptoms than previously reported for HPeV-4 [13], [14]. Prior to this study, there
Samples
Three HPeV-4 viruses FI121236, FI121290 and FI121301 were isolated from stool and serum samples of three patients (described earlier [13], [14]). All patients were hospitalized with suspected sepsis in Helsinki, October 2012. Children were aged 1–2 months, two were boys and one girl. The viruses were isolated and passaged 1–2 times in human colon adenocarcinoma cells (HT-29, ATCC) prior to viral RNA extraction with QIAamp Viral RNA kit (Qiagen) according to the manufacturer’s instructions.
Complete coding region sequences of the Finnish HPeV-4 isolates
An almost complete genome sequence, approximately 7200 nucleotides long (excluding only about 70 nucleotides from the 5′ end) was determined for HPeV-4 isolates FI121236, FI121290 and FI121301. The nucleotide sequences of these isolates were 99.8% similar to each other and therefore clustered closely together in the sequence analysis independent of the region under observation. These isolates can be considered to be of one strain, which circulated in the Helsinki region in fall 2012 causing
Discussion
This study presents complete coding sequences for three HPeV-4 isolates, that caused sepsis-like disease in Finnish infants in autumn 2012 [13], [14]. The sequencing of complete coding regions allowed analysis for their phylogenetic relations and recombination. Four main observations were made: 1) In the P1 and P2 regions, the Finnish HPeV-4 isolates were highly similar to the HPeV-4 strain isolated in the Netherlands in 2002; 2) the Finnish isolates had a 3 nucleotide deletion compared with
Funding
This work was financially supported by the Jane and Aatos Erkko Foundation, and HUSLAB (grant no. TYH2011305; Helsinki University Hospital, Finland).
Competing interests
None declared
Ethical approval
Not required, all clinical samples were analyzed anonymously encoded.
Acknowledgments
Anni Kauppinen is thanked for technical assistance. CSC − IT Center for Science Ltd. (Espoo, Finland) is acknowledged for the allocation of computational resources. The Finnish institute of Molecular Medicine (FIMM, Helsinki, Finland) is thanked for technical assistance.
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These authors contributed equally.