Page 225 - Avian Virology: Current Research and Future Trends

218 | Zheng

structural protein VP2 and the non-structural protein VP5 are massive apoptotic cell death (Cubas-Gaona et al., 2018), suggest-
the weapons employed by IBDV to induce the programmed cell ing that the IFN-α expression exacerbates apoptosis induced by
death process. To be noted, among five viral proteins of IBDV, virulent IBDV. From the perspective of viral evolution, a strong
VP2 and VP5 act as apoptosis inducers, but each of them only inflammatory response of host does not favour the survival of
make a partial contribution to IBDV-induced apoptosis (Li et IBDV. Tumour necrosis factor (TNF)-induced NF-κB signalling
al., 2012; Qin et al., 2017). Other factors might be also involved is an essential portion of innate immune response in host to viral
in this apoptotic process. Recently it was found that the addi- infection (Chen et al., 2003; Huang et al., 2003). It was reported
tion of IFN-α to infected cell cultures early after IBDV infection that proinflammatory cytokine TNF-α had been detected in the
drives massive apoptotic cell death (Cubas-Gaona et al., 2018). tissues of IBDV infected chickens (Zhang et al., 2011), suggesting
This findings remind us of an interesting report published as that TNF may induce inflammatory response in IBDV infected
early as 1979 that infection of chicken with IBDV induced IFN host. Li and colleagues found that IBDV infection inhibits
expression, and that the amount of IFN in the serum of chickens TNF-induced expressions of IFN-α, IFN-β and NF-κB at the
infected with pathogenic IBDV strain was much greater than that transcriptional level in host cells, and expression of VP4 in cells
of chicken with attenuated IBDV infection, suggesting that apop- inhibits TNF-induced activation of IFN-α, IFN-β and NF-κB pro-
tosis is attributed to the virulence of IBDV that helps the virus moters (Li et al., 2013). Furthermore, their data show that VP4 is
to survive in host cells. In addition, some microRNAs might play involved in IBDV-mediated suppression of IFN-α via interaction
roles in IBDV-induced apoptosis. Investigation into the role of with GILZ, a suppressor of NF-κB signalling. A recent publication
microRNAs in cell response to IBDV infection may be of help to has uncovered the mechanism underlying VP4-induced suppres-
the complete understandings of IBDV-induced apoptosis. sion of IFN-α, which shows that VP4 suppresses type I interferon
expression via inhibiting K48-linked ubiquitylation of GILZ, thus
Employment of autophagy allowing GILZ to avoid being degraded via ubiquitin-proteasome
Autophagy is a fundamental intracellular homeostatic process pathway and to suppress NF-κB-regulatory expression of IFN-α
that sequesters and removes unwanted cellular components such (He et al., 2018). As type I interferon is a critical anti-IBDV
as protein aggregates and damaged or superfluous organelles cytokine (O’Neill et al., 2010), VP4, via engagement with GILZ
by degrading them into amino acids, which are subsequently to suppresses type I interferon response, provide favourable con-
recycled back into the cytoplasm for reuse (Gatica et al., 2018). ditions for viral survival and replication in cells. A recent report
Autophagy can also sequester intracellular parasites and mediate indicates that a chicken microRNA (gga-miR-142-5p) attenuates
their destruction, playing important roles in innate and adaptive IRF7 signalling and promotes replication of IBDV by directly
immunity (Puleston and Simon, 2014). Viruses have developed targeting the chMDA5′s 3′ untranslated region (Ouyang et al.,
diverse strategies for evading or utilizing autophagy for survival. 2018). It seems that IBDV infection suppresses type I interferon
Up to now, there are only two reports available regarding the role expression via viral component VP4 and cellular miRNA-142-5p
of autophagy in IBDV infection, but the information from these as well. However, the mechanism of IBDV-mediated cellular
reports is interesting. It was found that the interaction of IBDV miRNA expression is currently unclear.
VP2 with virus receptor heat shock protein 90 (HSP90AA1) trig-
gered the autophagy, which was proposed to be the host defence Innate immune response of host to IBDV
against the infection since it inhibited the virus replication (Hu et infection
al., 2015). However, the other report shows that IBDV subverts Innate immunity is the first line of host defence against patho-
autophagic vacuoles to promote viral maturation and release, sug- genic infection. With a wide spectrum of defence mechanisms
gesting that IBDV may employ autophagy for survival (Wang et against pathogens, avian innate immune system consists of a vari-
al., 2017). It seems that cellular autophagy is employed by IBDV ety of immune effector cells, proteins and antimicrobial peptides
for its survival in host cells. The exact role of autophagy in cell (Cuperus et al., 2013). Defensins, a family of small antimicrobial
response to IBDV infection needs further clarifying. peptides with a characteristic β-sheet-rich fold and a framework
of six disulfide-linked cysteines (Ganz et al., 1990; Kagan et al.,
Suppression of type I interferons 1994; Ganz, 2003), exist in all species of animals, constituting
Type I interferons, including interferon alpha (IFN-α) and inter- a major part of innate immunity against pathogens. In addition
feron beta (IFN-β), play an important role in innate immunity to antimicrobial activity, defensins are also involved in immu-
against viral infection (Wang et al., 2010). Without exception, nomodulation (Ganz, 2003; Cuperus et al., 2013). Currently at
IFN-α has a strong anti-IBDV activity in vitro and in vivo assays least 25 different chicken β-defensins have been detected in chick-
(Mo et al., 2001; O’Neill et al., 2010). It was found as early as 1979 ens (Lynn et al., 2007; Hellgren and Ekblom, 2010; Cuperus et
that infection of chicken with IBDV induced IFN expression, and al., 2013). As the antimicrobial activity of β-defensins is primarily
the amount of IFN in the serum of chicken infected with patho- attributed to its induction of pore formation in membranes to kill
genic IBDV strain was much greater than that of chicken with pathogens, including Gram-positive and -negative bacteria, fungi
attenuated IBDV infection (Gelb et al., 1979), indicating that and even enveloped viruses (Ganz, 2003; Cuperus et al., 2013),
IBDV-induced IFN expression involves the virulence of IBDV IBDV, as a non-enveloped dsRNA virus, is not so much directly
strain. Recently it was demonstrated that the addition of IFN-α affected by β-defensins. Interestingly, it was found that immuniza-
to the infected cell cultures early after IBDV-infection drives tion of chickens with a DNA vaccine encoding IBDV VP2 gene