Full genome sequence analysis of parechoviruses from Brazil reveals geographical patterns in the evolution of non-structural genes and intratypic recombination in the capsid region

Abstract

Due to high genome plasticity, the evolutionary fate and geographical history of picornaviruses is hard to follow. Here, we determined the complete coding sequences of eight human parechoviruses (HPeV) of types 1, 5 and 6 directly from clinical samples from Brazil. The capsid genes of these strains were not remarkably different from European, North American and Japanese HPeV. Full genome analysis revealed frequent intertypic recombination in the nonstructural genome region. In addition, evidence of recombination between viruses of the same type in the capsid-encoding genome region among HPeV1 and HPeV4 was obtained. Bayesian phylogenetic analysis indicated that strains without evidence of recombination with each other in any genome region were separated by no more than 35 years of circulation. Interestingly, in the 3C gene, all Brazilian parechoviruses grouped together regardless of serotype. The most recent common ancestor of these strains dated back 108 years, suggesting long-term endemicity of this particular P3 genome lineage in South America. Our results support the idea that picornavirus replicative genes acquire capsid proteins introduced by new strains. Under certain epidemiological conditions, replicative genes may be maintained in circumscript geographical regions. INTRODUCTIONHuman parechoviruses (HPeV) are small non-enveloped viruses that define a genus of the family Picornaviridae. Their positive-sense RNA genome encodes a single polyprotein that is cleaved into three structural proteins, VP0, VP3 and VP1 (defining the P1 genome region), and seven non-structural proteins, 2A-2C (P2) and 3A-3D (P3). The first two HPeV serotypes were isolated in the 1950s and designated echovirus 22 and 23. In the 1990s, parechoviruses were reclassified into a new genus based on their distinct genome organization (Hyypiä et al., 1992). High prevalence of HPeV was not truly appreciated until the last few years. Recently, HPeVs were shown to be highly diverse, with up to 14 provisionally assigned types (AlSunaidi et al., 2007;Benschop et al., 2008a; Drexler et al., 2009;Ito et al., 2004; Kim Pham et al., 2010;Li et al., 2009;Watanabe et al., 2007). HPeV also proved highly prevalent in the human population, with seropositivity rates reaching 88 % at the age of 2 years (Joki-Korpela & Hyypiä, 1998;Takao et al., 2001), and an important cause of meningitis and sepsis-like disease of newborns (Baumgarte et al., 2008; 3These authors contributed equally to this work.The GenBank/EMBL/DDBJ accession numbers for the sequences reported in this paper are HQ696570-HQ696577. Wolthers et al., 2008). In general, recent reports showed that epidemiological and clinical features of HPeV are similar to the most common picornavirus genus, Enterovirus. HPeV genetic and evolutionary properties also resemble those of enteroviruses. They feature both high mutation rate (Faria et al., 2009) and frequent natural recombination (Benschop et al., 2008bCalvert et al., 2010;Williams et al., 2009;Zoll et al., 2009). Unfortunately, analyses of re...

An outbreak of severe infections among Australian infants caused by a novel recombinant strain of human parechovirus type 3

“…This is of significance as later studies have indicated that recombinants of HPeV3 may only emerge every 20 years or so, whereas recombinant strains of HPeV1, 2, 4, 5 and 6 appear to emerge roughly every 4 years192425262728. Some of those studies also looked at sequence variation in the structural region of HPeV1 and HPeV3 and estimated a substitution rate around 0.72% per year for HPeV1 and only 0.28–0.37% per year for HPeV31924.…”

“…Like other picornaviruses, recombination of HPeV often involves breakpoints at the very end of VP1 and thus may remove or add the RGD motif, or alternatively occur downstream in the non-structural coding region81920212223. Studies have indicated that recombinants of HPeV3 with other types may emerge less frequently and suggested that this may be due to a different cell tropism of HPeV3 compared to HPeV1, 2, 4, 5 and 6819242526272829.…”

African Non-Human Primates Host Diverse Enteroviruses

“…Genome walking was performed for the three samples as described previously [47, 48]. To obtain the complete genome, partial region of the 5’-UTR, VP2, VP1 and 3D were amplified using previously published assays [35–37].…”

The Complete Genome Sequence of a Human Parechovirus from a Child with Diarrhea in China Revealed Intertypic Recombination

“…One potential recombination event was found which occurred between the lineage of HPeV5 represented by the strain Br/53/2006 (HQ696575) and the lineage of HPeV1 represented by the strain BNI-788st (EF051629). Br/53/2006 was identified in fecal samples from patients with acute diarrhea in Brazil (11), while BNI-788st was isolated from the stool sample of a German patient in Hamburg (12). Bootscan analysis showed one potential breakpoint located at the border between the P2 and P3 regions.…”