Avian picornaviruses: Molecular evolution, genome diversity and unusual genome features of a rapidly expanding group of viruses in birds

Highlights

• The phylogenetic and genome organization and diversity of avian viruses were remarkable.

• The variability of multicistronic 2A genome of avian picornaviruses regions were analyzed.

• Several conserved RNA structures among avian and non-avian picornaviruses were detected.

• Five avian picornavirus clusters located in every main picornavirus lineage were established.

• The taxonomy, phylogenetic/genomic diversity of avian picornaviruses were summarized.

Abstract

Picornaviridae is one of the most diverse families of viruses infecting vertebrate species. In contrast to the relative small number of mammal species compared to other vertebrates, the abundance of mammal-infecting picornaviruses was significantly overrepresented among the presently known picornaviruses. Therefore most of the current knowledge about the genome diversity/organization patterns and common genome features were based on the analysis of mammal-infecting picornaviruses. Beside the well known reservoir role of birds in case of several emerging viral pathogens, little is known about the diversity of picornaviruses circulating among birds, although in the last decade the number of known avian picornavirus species with complete genome was increased from one to at least 15. However, little is known about the geographic distribution, host spectrum or pathogenic potential of the recently described picornaviruses of birds. Despite the low number of known avian picornaviruses, the phylogenetic and genome organization diversity of these viruses were remarkable. Beside the common L-4-3-4 and 4-3-4 genome layouts unusual genome patterns (3-4-4; 3-5-4, 3-6-4; 3-8-4) with variable, multicistronic 2A genome regions were found among avian picornaviruses. The phylogenetic and genomic analysis revealed the presence of several conserved structures at the untranslated regions among phylogenetically distant avian and non-avian picornaviruses as well as at least five different avian picornavirus phylogenetic clusters located in every main picornavirus lineage with characteristic genome layouts which suggests the complex evolution history of these viruses. Based on the remarkable genetic diversity of the few known avian picornaviruses, the emergence of further divergent picornaviruses causing challenges in the current taxonomy and also in the understanding of the evolution and genome organization of picornaviruses will be strongly expected. In this review we would like to summarize the current knowledge about the taxonomy, pathogenic potential, phylogenetic/genomic diversity and evolutional relationship of avian picornaviruses.

Introduction

The members of the family Picornaviridae belong to the most diverse group of viruses with a positive sense, single-stranded RNA genome. In general, the 6.7–9.8 kb polyadenylated genome of picornaviruses predominantly consists of a single viral polyprotein coding region flanked by highly structured 5′ and 3′ untranslated regions (UTRs), although a canine picornavirus with multiple Open Reading Frames (ORFs) have been reported recently (Woo et al., 2012). The viral polyprotein is co- and post-translationally processed into multiple capsid monomers: VP0 (mainly cleaved to VP4 and VP2), VP3 and VP1, and variable number of non-structural proteins: 2A, 2B, 2C^hel, 3A, 3B^VPg, 3C^pro and 3D^pol. The presence of a leader (L) protein upstream of the capsid proteins is also common among the known picornaviruses (Racaniello, 2007, Knowles et al., 2011).

Over half of the known human pathogens, including the emerging viral pathogens were suspected to be zoonotic in origin (Taylor et al., 2001). Birds are well known reservoirs of many emerging viral pathogens including the influenza A viruses of family Orthomyxoviridae, Newcastle Disease virus (Paramyxoviridae); West Nile virus (Flaviviridae) and Japanese encephalitis virus (Flaviviridae) in humans (Stallknecht et al., 2007, Leighton and Heckert, 2007, McLean and Ubico, 2007). Beside the zoonotic viruses there is a growing list of pathogens of economically important domestic birds circulating among wild, free-ranging avian species including Duck plague (caused by Anatid herpesvirus 1), reoviruses or Mycoplasma gallisepticum (Hansen and Gough, 2007, Hollmén and Docherty, 2007, Luttrell and Fischer, 2007). Despite the continuous increase of known picornaviruses, little is known about the diversity, host spectrum or pathogenic potential of picornaviruses circulating in domestic and free-ranging birds. At present, the Picornaviridae family consists of 46 species grouped into 26 genera and further 18 candidate species which may belonged to at least 7 novel genera (Knowles et al., 2014) all of which were identified from different vertebrates mainly from mammals. Most picornaviruses – thought to – have a narrow host species spectrum with the exception of encephalomyocarditis virus (EMCV) which could infect multiple mammal species of five different orders (Lewis-Rogers and Crandall, 2010).

Based on the estimated number of mammal species (c.a 5500; Wilson and Reeder, 2005) compared to the number of birds (c.a 9800; Clements, 2007) or reptiles (c.a. 9900; Uetz and Hošek, 2014) the abundance of mammal-infecting picornaviruses was significantly overrepresented (>80%) among the known picornaviruses. Until 2006, only one complete genome sequence of non-mammal picornavirus, avian encephalomyelitis virus 1 (AEV-1), identified from domestic chicken (Gallus gallus domesticus) was known (Marvil et al., 1999). At the end of 2000s, only further two non-mammal picornavirus species – the Duck hepatitis A virus (DHAV, formerly Duck Hepatitis virus 1) and the Avian sapelovirus 1 (ASV-1) (formerly Duck picornavirus TW90A) both isolated from domestic duck (Anas platyrhynchos) – were known (Kim et al., 2006, Tseng and Tsai, 2007). The advance of different PCR-based techniques and the robust next-generation sequencing (NGS) methods accelerated the pace of virus discovery (Delwart, 2012, Chiu, 2013) including the description of novel picornaviruses in wide range of animal species. Beside the growing number of avian picornaviruses the identification of picornaviruses from lower vertebrates (e.g. fish, reptile) was recently started (Fichtner et al., 2013, Barbknecht et al., 2014, Lange et al., 2014, Heuser et al., 2010).

In this review, we would like to summarize the current knowledge about the avian picornaviruses with a focus on the (i) diversity, taxonomy, host species spectra, geographic distribution and pathogenic potential of avian picornaviruses; (ii) the genome organization layouts and phylogenetic/evolutional relationship of avian picornaviruses and (iii) the analysis of the 5′/3′ UnTranslated Regions (UTRs) particularly the presence of highly conserved sequence motifs/structures. We also would like to demonstrate the phylogenetic/genomic diversity of avian picornaviruses compared to the known mammal-infecting picornaviruses in evolutional point of view.