Refereed journal article or data article (A1)

Recombination Events and Conserved Nature of Receptor Binding Motifs in Coxsackievirus A9 Isolates

List of Authors: Eero Hietanen, Petri Susi

Publisher: MDPI AG

Place: Basel

Publication year: 2020

Journal: Viruses

Journal acronym: Viruses

Volume number: 12

Issue number: 1

Number of pages: 15

eISSN: 1999-4915



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Coxsackievirus A9 (CVA9) is an enterically transmitted enterovirus and
one of the most pathogenic type among human enteroviruses. CVA9 isolates
use a distinctive RGD (Arg-Gly-Asp) motif within VP1 capsid protein
that defines its ability to bind to integrin receptor(s) for cellular
entry. To investigate CVA9 evolution and pathogenicity, genetic
relationships and recombination events were analyzed between 54 novel
clinical isolates of CVA9, as well as 21 previously published full
length CVA9 sequences from GenBank. Samples were investigated by partial
sequencing of the novel VP1 and 3Dpol genes, as well as including the
corresponding areas from GenBank sequences. Phylogenetic analyses were
combined with clinical data in a further attempt to analyze whether
sequence evolution reflects CVA9 pathogenicity in the phylogenies.
Furthermore, VP1 gene was also analyzed for receptor binding sites
including the RGD motif and the putative heparan sulfate (HS) site.
Analysis of the 559-nucleotide-long VP1 sequences identified six clades.
Although most of the strains within each clade showed geographical
clustering, the grouping pattern of the isolates in the analysis of the
VP1 gene was strikingly different from grouping of 3Dpol, which suggests
that recombination events may have occurred in the region encoding the
nonstructural proteins. Inclusion of clinical data did not provide any
evidence of symptom based phylogenetic clustering of CVA9 isolates.
Amino acid sequence analysis of the VP1 polypeptide demonstrated that
the RGD motif was fully conserved among the isolates while the putative
HS binding site was only found in one isolate. These data suggest that
integrin binding is essential for virus tropism, but do not explain the
symptom repertoire.

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Last updated on 2022-07-04 at 17:44