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targeting the viral genome and/or targeting the negative regula- humoral immune response because high levels of specific anti-
tors for the antiviral signalling pathways. Thus, gga-miR-130b, bodies against IBDV can be detected in the serum of vaccinated
gga-miR-454 and gga-miR-155 play crucial roles in host defence chickens, and the titres of antibodies were correlated to the pro-
against IBDV infection. On the contrary, gga-miR-9* inhibits IFN tection (Nakamura et al., 1994), indicating that humoral immune
production by targeting interferon regulatory factor (IRF) 2 to response play a crucial role in protecting chickens. Although live
promote IBDV replication (Ouyang et al., 2015), gga-miR-2127 attenuated IBDV vaccine strains caused transient depletion of the
down-regulates chicken p53 (chp53) expression by targeting bursal follicles, which was followed by B-cell repopulation and
its 3′UTR, dampens chp53-mediated anti-IBDV response and histological regeneration, the repopulated B-lymphocytes in the
facilitates IBDV replication (Ouyang et al., 2017), and gga- bursa were functionally active and the bursa was serving again
miR-142-5p attenuates IRF7 signalling and promotes IBDV as an efficient primary lymphoid organ providing an appropriate
replication by directly targeting the chMDA5′s 3′ untranslated microenvironment for B-cell development (Iván et al., 2001).
region (Ouyang et al., 2018), suggesting that gga-miR-9*, gga- Based on clinical observations, IBDV-infected chickens show
miR-2127 and gga-miR-142-5p inhibit host defence and favour immunosuppression primarily during the period of viral replica-
viral replication. It seems that different miRNAs may have varied tion and before the complete repopulation of bursal follicles with
or even opposite effects on host response to IBDV infection (Fig. B lymphocytes, but once fully recovered, the chickens have high
7.4). However, the exact mechanisms underlying the initiation of titres of specific antibodies against IBDV in the serum and display
miRNA expressions and regulation of cell response by miRNA to normal immune response to other pathogens. However, if the
IBDV infection are still not very clear. virus remains circulating in the infected flocks, a certain number
of chickens may suffer from subclinical infections, leading to
Adaptive immune response of host to IBDV immunosuppression.
infection
Adaptive immune response is mainly carried out by B and T Cell-mediated immune response to IBDV
lymphocytes. The primary target cells of IBDV serotype I strains Thymus is the central immune organ for the development and
are the proliferating B lymphocytes in the BF, a central immune maturation of T lymphocytes. Thymectomized chickens had
organ of poultry that is responsible for the development and mat- poor humoral response to inactivated IBDV vaccines and could
uration of B lymphocytes. As such, IBDV-induced apoptosis in B not be well protected by vaccination, indicating that T helper
lymphocytes directly result in the rapid loss of B cells in the BF, cells are required for the activation of B lymphocyte producing
leading to the destruction of chicken immune system. In addition protective antibodies (Rautenschlein et al., 2002b). Infection of
to the rapid loss of B cells in the BF, chicken spleen and peripheral chickens with IBDV serotype I strains induces expressions of
blood lymphocytes undergo apoptosis during IBDV infection. T proinflammatory cytokines IL-1β, IL-6 and CXCLi2 as well as
lymphocytes appear non-susceptible to IBDV during infection Th1 cytokines IL-2 and IFN-γ, but not type I interferons, which
(Ramm et al., 1991) but play a critical role in protecting chickens indicates that a pro-inflammatory response is induced and a cell-
from IBDV infection. mediated immune response is also elicited (Eldaghayes et al.,
2006). However, CD4 or CD8 T lymphocyte, unlike B cell, is not
Humoral immune response to IBDV infected by IBDV, but could be activated via TCR recognition of
BF, as a central immune organ of poultry, is responsible for the viral antigenic epitopes presented by MHC (chicken MHC is also
development and maturation of B lymphocytes, thus any damage designated as B)-II or MHC-I of antigen presenting cell (APC)
to BF would affect humoral immune response of chickens to (such as macrophage, dendritic cell or B cell) that internalizes
antigens. As BF serves as the target organ of IBDV, infection of IBDV via macropinocytosis or phagocytosis. The activated CD4
chickens with IBDV serotype I strains induces severe apoptosis in or CD8 T lymphocytes, particularly cytotoxic T lymphocytes
proliferating B cells, which directly damages BF. The experimen- (CTL, an activated CD8T-cell), proliferate exponentially and
tal evidence shows that bursectomized chickens did not become yield numerous progeny effector T-cells that act like fully armed
sick after infection with a lethal dose of highly virulent IBDV soldiers. These CTL soldiers recognize and destroy IBDV-
strain Cu-1 (Käufer and Weiss, 1980; Schat et al., 1981), indicat- infected cells so that the invading virus could be exposed and
ing that BF is required for IBDV infection and pathogenesis. The neutralized by the circulating specific antibodies. It was found
incubation period of experimental infection with virulent IBDV that chickens with compromised cell-mediated immunity had an
serotype I strains is usually around 2–3 days, followed by an increased IBDV antigen load, abrogated inflammatory response
acute phase of the disease that lasts around one week. During this and reduced apoptosis in bursa and cytokine expressions(IL-2
period, BF is severely damaged, resulting in suppressed immune and IFN-γ) as compared with the T-cell-intact control chickens,
response and increased susceptibility to the secondary microbial but their intrabursal T-cells promote bursal tissue damage and
infection in recovered chickens (Sharma et al., 2000; Subler et al., delay tissue recovery compared with that of T-cell-intact control
2006; Mahgoub et al., 2012). Chickens that survived the acute chickens (Rautenschlein et al., 2002a), indicating that T-cells
phase had detectable specific antibodies against IBDV in the are involved in inflammatory response in chicken BF to IBDV
serum, suggesting that humoral immune response was elicited in infection. Furthermore, adaptation of IBDV to macrophages
chickens with IBDV infection. Immunization of chickens with a enhanced the ability of the virus to induce cell-mediated immune
live attenuated IBDV strain or inactivated vaccine mounts a strong response in chickens (Khatri and Sharma, 2008), suggesting that