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Virus characteristics

Classification and structure of IBDV
IBDV is a non-enveloped double-stranded (ds) RNA virus.
The viral particle is a icosahedral capsid with a diameter of
about 60 nm (Dobos et al., 1979; Müller et al., 2003). As the
virus contains two segments of double-stranded RNA (A and
B) (Azad et al., 1985), it is classified into the genus Avibir-
navirus, family Birnaviridae. Whereas the short RNA, segment
B (2.8 kb) encodes VP1, a RNA-dependent RNA polymerase
(RdRp) (Morgan et al., 1988; von Einem et al., 2004), segment
A, the large molecule (3.17 kb) contains two partially overlap- Figure 7.1 Schematic illustration of IBDV virion particle. IBDV
ping open reading frames (ORFs) (Hudson et al., 1986; Spies et contains two segments of double-stranded RNA (A and B). Segment
B (Seg B), the short RNA (2.8 kb), encodes VP1, a RNA-dependent
al., 1989). The first ORF encodes the non-structural viral pro- RNA polymerase (RdRp) and genome-linked protein of IBDV.
tein 5 (VP5) (Mundt et al., 1995; Lombardo et al., 2000), and Segment A (Seg A), the large molecule (3.17 kb), contains two
the second one encodes a 110-kDa polyprotein precursor that partially overlapping open reading frames (ORFs). The first ORF
can be cleaved by the proteolytic activity of VP4 to form viral encodes non-structural protein VP5, and the second one encodes
a 110-kDa polyprotein precursor that can be cleaved to form viral
proteins VP2, VP3, and VP4 (Hudson et al., 1986; Jagadish et proteins VP2, VP3, and VP4. VP1 is involved in the efficiency of
al., 1988; Kibenge et al., 1991). VP2 and VP3 are the major viral replication and modulates the virulence. VP2, a structural
structural proteins, constituting 51% and 40% of the virion, protein, acts as a viral ligand binding to the receptor on host cell
respectively (Dobos et al., 1979; Todd and McNulty, 1979; membrane for virus attachment, an initial step of IBDV infection.
VP3, a scaffold protein, interacts with the structural protein VP2 and
Tacken et al., 2000). VP4 is a classical cis-cleavage protein and recruits genome dsRNA and VP1 to form a ribonucleoprotein (RNP)
its trans-activity is present but acts later in the life cycle of a complex, playing a critical role in virus assembly.
double-stranded RNA virus (Birghan et al., 2000; Lejal et al.,
2000). VP4 is able to cleave in trans and is responsible for the
interdomain proteolytic autoprocessing of the pVP2-VP4-VP3 Genetic variation and virulence of IBDV
polyprotein encoded by RNA segment A into pVP2 precur- An eminent feature of RNA virus is the genetic variation due
sor (512 residues, 54.4 kDa) as well as VP4 (28 kDa) and VP3 to the low proof-reading activity of their viral replicases. As a
(32 kDa) (Lejal et al., 2000; Wang et al., 2015). Both VP4 and dsRNA virus, IBDV displays high genetic variations mostly in
the puromycin-sensitive aminopeptidase (PurSA) cleave the VP2 hyper variable region (HVR) that lies in the central region
pVP2 at its C-terminus to generate the intermediate pVP2 (452 between residues 212 and 332 aa, in which most of the amino acid
residues) (Irigoyen et al., 2012), which is further processed substitutions occurs (Vakharia et al., 1994a), leading to antigenic
by the VP4 viral protease and by VP2 itself to generate the variation, and this region is also related to the viral attachment
mature VP2 (441 residues) (Irigoyen et al., 2009). The mature since VP2 induces neutralizing antibodies. Sequencing analysis of
VP2 with a variable amount of pVP2 (452 residues) and VP3 VP2 is very helpful to determine if the IBDV strain of interest is
assemble the single shelled capsid of IBDV (Saugar et al., 2005; a ‘classical’, vvIBDV or variant strains because of high sequence
Luque et al., 2007). VP3 acts as a scaffold protein that binds diversity in the HVR of serotype 1 (Zierenberg et al., 2000;
both the viral double-stranded RNA and VP1 (Lombardo et Banda and Villegas, 2004; Owoade et al., 2004; Shehata et al.,
al., 1999), and the interaction of VP1 and VP3 is sufficient 2017). Interestingly, attenuation of vvIBDV Gx strain via passage
to form a virus-like particle (VLP) insect cells (Maraver et al., in specific-pathogen free (SPF) chicken embryos and in chicken
2003). As shown in Fig. 7.1, VP3 interacts with both VP2 and embryo fibroblast (CEF) cell cultures indicates that the changes
VP1, forming virion particle. VP5, a highly basic, cysteine-rich, in amino acid sequences of VP2, VP3 and VP5 occurred at 9 pas-
17 kDa non-structural (NS) protein is conserved among all sages in CEF (CEF-9) associated with a remarkable reduction in
serotype I of IBDV strains. This protein is not required for the virulence of Gx strain (Wang et al., 2004, 2007). However, the
viral replication (Mundt et al., 1997; Qin et al., 2010), but can exact virulence factor of IBDV needs to be clarified because IBDV
be detected in IBDV-infected cells (Mundt et al., 1995, 1997; virulence seems to be affected by several viral components such
Lombardo et al., 2000). Among the viral proteins of IBDV, VP2 as VP1 (Liu and Vakharia, 2004; Yu et al., 2013), VP2 (Toroghi et
and VP5 are major factors responsible for IBDV-induced apop- al., 2001; van Loon et al., 2002), VP3 (Boot et al., 2002), and VP5
tosis (Fernández-Arias et al., 1997; Yao and Vakharia, 2001; (Qin et al., 2009).
Li et al., 2012), while VP3 and VP4 are more likely involved Using the reverse genetics system, it was found that the VP1
in suppression or evasion of host immune response (Li et al., protein of IBDV is involved in the efficiency of viral replication
2013; Ye et al., 2014; He et al., 2018). Although the genome and modulates the virulence in vivo (Liu and Vakharia, 2004).
of IBDV encodes a limited number of components, these viral Substitution of amino acid (V4I) of VP1 attenuates viral patho-
components may perform multiple functions in host via inter- genicity and reduces viral replication in SPF chickens but increases
action with cellular target proteins. viral replication in CEF cells (Yu et al., 2013), indicating that VP1