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is highly specific, probably depending on the conserved terminal for fusion of host cells and syncytium formation (Bodelón et
sequences at both ends of the RNA segments, resulting in the al., 2001; Shmulevitz et al., 2002; Barry and Duncan, 2009). It
packaging of one copy of each genome segment per particle. increases plasma membrane permeability, and is therefore a
Reovirus replication results in intracytoplasmic inclusion bodies viroporin (Bodelón et al., 2002; Wu et al., 2016). It also induces
(viroplasms). These inclusion bodies are the sites of viral replica- apoptosis of the host cell (Salsman et al., 2005; Wu et al., 2016).
tion and assembly (Shao et al., 2013). P17, a membrane associated non-structural protein functions as
The avian reovirus replication cycle was described by a shuttle protein, moving between nucleus and cytoplasm con-
Benavente and Martínez-Costas (2007). Avian reovirions attach tinuously, participating in cellular nuclear processes such as host
to cell surface receptors through the cell attachment protein, σC, cell translation and cell cycle autophagosome formation, which
a minor component of outer capsid, which is encoded on the favour avian reovirus replication (Costas et al., 2005; Liu et al.,
S1 segment. Virus entry to the cytoplasm by receptor-mediated 2005; Ji et al., 2009; Chulu et al., 2010; Chi et al., 2013; Huang et
endocytosis involves interaction and conformational changes in al., 2015; Chiu et al., 2016).
µB (O’Hara et al., 2001), a major outer capsid protein encoded
by M2 segment. Intraendosomal reovirion uncoating is followed
by the release of transcription-competent core particles into the Genetics and reverse genetics
cytosol. Transcription of the dsRNA genome segments produces
all 10 viral mRNAs, which have a dual function in the infected Current status
cell: (i) they are translated into viral proteins at the ribosomes; (ii) As reviewed above, the functions of proteins encoded by each seg-
they are recruited into newly formed core or subcore particles and ment of the avian reovirus genome have been studied extensively.
used as templates for the synthesis of the viral minus strands, thus The evolutionary relationships among avian reoviruses have been
forming progeny genomes. The λA protein, a major core protein studied by phylogenetic analysis. Genotype/phenotype correla-
that forms the inner core shell and is encoded on the L1 segment tion requires the use of reverse genetics to introduce mutations
(Guardado-Calvo et al., 2008), serves as a scaffold during the ini- into viral capsid and non-structural components to study viral
tial stages of viral morphogenesis. The µNS protein encoded on protein-structure activity relationships in replication process and
segment M3 forms viral factory scaffold (matrix) and temporally pathogenesis. Reverse genetics can also be exploited to engineer
and selectively controls the recruitment of specific viral proteins recombinant reoviruses for vaccines containing specific changes
to viral factories (Tourís-Otero et al., 2004; Brandariz-Nuñez targeted for attenuation, and for oncolytic applications. How-
et al., 2010) and acts as an RNA chaperone facilitating specific ever, in family Reoviridae, the application of reverse genetics has
RNA–RNA interactions between genomic precursors during been hampered by the nature of the genome (10 to 12 dsRNA
segment assortment and packaging (Borodavka et al., 2015). The segments densely packed within the viral particle) and how it is
mature reovirions that form exit the infected host cell following replicated (within a subviral structure) (Troupin et al., 2018).
cell lysis (Benavente and Martínez-Costas, 2007). There is currently one published report of reverse genetics using
avian reoviruses (Wu et al., 2018); the application of this system
Effects on the host cell will significantly increase our understanding of avian reovirus
Reoviruses in the genera Orthoreovirus and Aquareovirus are biology and disease.
the only known examples of non-enveloped viruses that induce
cell–cell fusion and syncytium formation (i.e. are fusogenic) Phylogenetic analysis
in virus-infected cells. The Orthoreovirus genus is divided into Avian reoviruses originating from different avian species, geo-
non-fusogenic (MRV) and fusogenic orthoreoviruses (NBV, graphical regions and even lesion type or pathogenicity can be
BRV, ARV, RRV, Broome Orthoreovirus BroV) (Duncan, 1999; shown to be genetically distinct (Gouvea and Schnitzer, 1982;
Thalmann et al., 2010) by possession of a fusion-associated small Liu and Giambrone, 1997; Le Gall-Reculé et al., 1999; Spackman
transmembrane (FAST) protein (also referred to as p10, p13, et al., 2005; Shivaprasad et al., 2009; Mor et al., 2013; Yun et al.,
p14, p15, p16 or p18 in the different reoviruses) (Shmulevitz and 2013; Sharafeldin et al., 2014, 2015; Sellers 2017). A phylogenetic
Duncan, 2000; Jansen van Vuren et al., 2016). Syncytia formation analysis, based on the sequences of the cell attachment protein
commences 10–12 hours post infection, resulting in a more rapid σC (encoded on S1 segment), grouped the avian reoviruses into
lytic response and enhanced kinetics of virus release (Attoui et five genotyping clusters, with the sequences of the Netherlands,
al., 2012). Some of the members of the Aquareovirus genus also Germany and Taiwan isolates being more dispersed than those
possess a FAST protein and induce syncytium formation. Most of the USA and Australia isolates (Kant et al., 2003) but without
recently, PRV has been shown to be closely related with recog- correlation of genotype and pathotype (Benavente and Martínez-
nized orthoreoviruses and its non-structural protein p13 is not a Costas, 2007). Liu et al. (2003), and Ayalew et al. (2017) who
FAST protein and is therefore non-fusogenic (Key et al., 2013). included 37 emerging variant ARV strains from Saskatchewan,
The non-structural proteins, p10 and p17, encoded by the Canada, reported six genotyping clusters or groups in the σC (S1)
first two cistrons of the tricistronic avian orthoreovirus S1 gene gene phylogenetic tree, but Liu et al. (2003) identified only three
(Bodelón et al., 2001; Shmulevitz et al., 2002) have significant in the σNS (S4) gene tree whereas Ayalew et al. (2017) found a
effects on the host cell that favour avian reovirus replication. 92–100% sequence identity in the σB (S2) gene, reflecting fre-
P10 is the FAST protein in avian reoviruses that is responsible quent gene reassortment among ARV isolates. For example, in the