Page 222 - Avian Virology: Current Research and Future Trends

Infectious Bursal Disease Virus | 215

Interaction of viral components with cellular expressed in the cytosol of infected cells and interact with cellular
proteins proteins to exert their specific functions. As the total number of
Once IBDV successfully infects cells, all viral protein components viral proteins encoded by IBDV genome is relatively limited, it
will be expressed to complete its replication cycle. As mentioned is very likely that these viral proteins perform multifunctional
above, IBDV genome comprises two segments of double-stranded jobs via binding to different cellular factors during IBDV infec-
RNA encoding five viral proteins, VP1–5. These viral proteins are tion (Qin and Zheng, 2017). As shown in Fig. 7.3, based on the

Figure 7.3 Schematic illustration of apoptosis and immunosuppression induced by viral proteins via interaction with cellular targets. Upon
IBDV infection, host cells express the viral proteins that play different roles via interaction with cellular targets during IBDV replication. VP5
inhibits apoptosis of host cells via interaction with p85alpha subunit of PI3K early after IBDV infection to allow sufficient time for IBDV
replication. As apoptosis is required for the spread of IBDV, VP5 induces apoptosis via interaction with VDAC2 by intrinsic apoptotic pathway
at a later phase of IBDV infection. Meanwhile, apoptosis induced by VP2 via interaction with ORAOV1 may also help IBDV spread. RACK1
favours IBDV growth by inhibiting apoptosis via interaction with both VDAC2 and VP5. VP4 suppresses expression of type I interferon by
host cells via interaction with GILZ to prevent GILZ from ubiquitin-mediated proteasomal degradation, allowing accumulation of GILZ, which
stops transcriptional regulators NF-kB and AP-1(?) from initiating the expression of type I interferon to favour IBDV replication. VP3 inhibits
recognition of dsRNA of IBDV by MDA5, a member of RLRs acting as pattern recognition receptors in the cytosol of host cells, to help IBDV
evade host immune response against IBDV infection. In addition, VP3 interacts with RPL18 and PRK, forming a complex and suppressing
type I IFN expression via inhibition of transcriptional regulators NF-kB and IRF3. VP1, a RNA-dependent RNA polymerase of IBDV, interacts
with carboxy-terminal domain of translational eukaryotic initiation factor (eif) 4AII, a host translation initiation factor. VP1 also interacts with
nuclear factor NF45, an RNA binding protein that regulates gene expression. The relevance of VP1 binding to eif 4AII or NF45 needs further
clarifying. Abbreviations: AP-1, activating protein-1; CARD, caspase activation and recruitment domain; eif, eukaryotic initiation factor;
GILZ, glucocorticoid-induced leucine zipper; IRF, interferon regulatory factor; JNK, c-Jun-N-terminal kinase; MAVS, mitochondrial antiviral
signalling protein; MDA5, melanoma differentiation-associated gene 5; Mito, mitochondrion; NF-kB, nuclear factor kappa enhancer binding
protein; ORAOV1, oral cancer overexpressed 1; PI3K, Phosphoinositol-3 kinase; PKR, double-stranded RNA-activated protein kinase;
RACK1, receptor of activated protein kinase C1; RLRs, rig like receptors; RPL18, ribosomal protein L18; VDAC2, voltage-dependent anion
channel 2.