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alone provided lower protection rate than that of immunization had stronger innate immune response accompanied by faster
with IBDV VP2 gene together with chicken beta-defensin-1 and more severe lesions and death after vIBDV infection than
(AvBD1) gene, indicating that AvBD1 has an adjuvant effect control chickens with less susceptibility, but no significant differ-
on improvement of the IBDV VP2-DNA vaccine effectiveness ences were observed between genetic backgrounds of chickens
(Zhang et al., 2010). Besides, oral administration of chicken intes- in induction of the IBDV-specific humoral response (Aricibasi et
tinal antimicrobial peptides (CIAMP) increased the anti-IBDV al., 2010), indicating that the disease outcome is primarily deter-
antibody titres in chickens after inoculation with IBDV vaccine, mined by the innate immunity rather than by adaptive immune
suggesting that CIAMP modulate the humoral immune response response of chickens with different genetic backgrounds. These
of chicken to IBDV (Yurong et al., 2006). Macrophage plays a observations are supported by the later findings that the genes
central role in innate immunity. Infection of chicken splenocytes encoding chicken PRRs, such as chTLR1 type 1 and type 2
with IBDV causes activation of macrophage, which enhances (Ruan and Zheng, 2011), chTLR2 type 1 and type 2 (Ruan et
production of NO, IL-8 and COX-2 by macrophages via the al., 2012b), and chTLR5 (Ruan et al., 2012a), are polymorphic in
p38 MAPK and NF-kappaB pathways (Khatri and Sharma, the PAMP-recognizing domains of PRRs among chicken breeds,
2006). The expression of inflammatory mediators (NO, IL-8 and which suggests that the sensitivity of chickens to recognizing the
COX-2) by macrophages enhances bursal inflammation during invading pathogens among chicken breeds varies. This informa-
IBDV infection. Interestingly, infection of avian macrophage tion provides an important clue to the consideration for future
cell line (NCSU) with classical IBDV (cIBDV) and antigenic poultry breeding and breed improvement. Furthermore, gga-miR-
variant IBDV (vIBDV) rendered the capability of progeny virus 142-5p, a microRNA of chicken, suppresses chMDA5 expression
from NCSU cell cultures to infect DF-1 cells, a chicken embryo and promotes IBDV replication in DT40 cells through an IRF7-
fibroblast cell line, only after one replication cycle in NCSU cells dependent pathway (Ouyang et al., 2018). Thus, recognition of
(Khatri and Sharma, 2007), suggesting that replication of IBDV dsRNA of IBDV by chMDA5 might be regulated by multiple
in macrophages altered tropism of progeny virus. The genetic factors. More efforts are encouraged to work on the mechanism
basis of altered tropism of progeny virus from NCSU cell cultures of sensing IBDV infection by chicken PRRs.
needs to be identified.
Roles of cellular microRNA (miRNA) in host
Recognition of PAMPs of IBDV by PRRs of response to IBDV infection
host cells miRNA is a large family of small non-coding RNAs of 20–24
Pathogen-associated molecular patterns (PAMPs) are distinct nucleotides that post-transcriptionally regulate eukaryotic gene
microbial structures recognized by host receptors termed expression by affecting degradation and translation of target
pattern-recognition receptors (PRRs) (Janeway, 1989). PRRs mRNAs. The biogenesis of miRNAs in animals involves several
serve as important sensors in recognizing invading pathogens processing steps and well-reviewed in the literature (Wang et
and initiating the innate immune response of host to pathogenic al., 2007; O’Connell et al., 2012; Clayton et al., 2018). Briefly,
infection. At least six families of PRRs have been identified in miRNAs are transcribed from the genome to create primary (pri-)
vertebrates, including Toll-like receptors (TLRs), the nucleotide miRNA, further processed into precursor miRNA (pre-miRNA)
oligomerization domain (NOD) proteins-like receptors (NLRs), by the nuclear RNase III enzyme Drosha and associated factor
the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), Pasha/DGCR8. These pre-miRNAs are then actively transported
C-type lectin receptors (CLRs), AIM2-like receptors (ALRs) by Exportin 5 (XPO5) and Ran-GTP to the cytoplasm, where
and cGAS-STING. These receptors either are membrane-bound they are further processed by the RNase III enzyme Dicer as
or exist in cytosol, recognizing specific structures of invading part of a protein complex that produces the mature miRNA. The
pathogens. The microbial structures are usually evolutionarily functional miRNA strand is then selectively loaded onto Argo-
conserved molecular components essential for pathogen survival naute protein and forms RISC along with other proteins such as
and not present in host, such as microbial nucleic acids, lipopoly- GW182. Mature miRNAs then guide the RISC to cognate target
saccharide (LPS), lipoproteins, bacterial flagellin, and yeast genes. Silencing occur by promoting deadenylation and mRNA
zymosan. Upon IBDV infection, host cell recognizes viral dsRNA degradation or translational repression. miRNAs bind to the
in the endosome by chicken TLR3 and in the cytosol by Mela- 3′UTR of a target gene by base pairing, acting as inhibitors of
noma Differentiation-Associated gene-5 (MDA5), a member of translation when the binding at the 3′UTR of target genes is only
RLRs, to initiate anti-viral immune response (Lee et al., 2014; partially complementary but as an inducer of mRNA degradation
Zhang et al., 2016; He et al., 2017). It was found that recognition when the binding complementarity is perfect. Under specific
of IBDV by chicken MDA5 sensor activates chMDA5-related conditions, miRNAs can activate translation by binding to non-
innate immune response genes (IRF-3, IFN-beta, PKR, etc.) and canonical sites in the 5′UTR of target genes. miRNAs are involved
up-regulates the expression of chicken major histocompatibility in various biological processes, including the development and
complex (MHC, chicken MHC is designated as B) class I (Lee differentiation of cancer (Lu et al., 2005), cell proliferation and
et al., 2014). However, IBDV VP3 protein competes strongly differentiation (Zhou et al., 2007; Trajkovski and Lodish, 2013),
with chMDA5 to bind dsRNA of IBDV to inhibit the antiviral cell cycle and apoptosis (Guo et al., 2009; Tian et al., 2017),
response via the MDA5-dependent signalling pathway (Ye et al., immunoregulation and viral infection (Zhu et al., 2015; Fu et
2014). Interestingly, chickens with high susceptibility to IBDV al., 2018a). Upon IBDV infection of DF-1 cells, 296 miRNAs