It has been proved that the resistance of chicken to MDV is influenced by different genetic backgrounds [29
]. And the chicken's different haplotypes of major histocompatibility complex (MHC) affect the resistance of chicken to disease. It have been demonstrated that the B21 and B19 haplotypes are associated with resistance and susceptibility MDV, respectively [30
]. Meanwhile, several quantitative trait loci (QTL) against to MDV within the chicken's genome had been identified using genetic markers [31
]. However, the underlying mechanism how genetic background influences the resistance of chicken to MDV remains unknown. In this study, two breeds, economic line-broilers and native line-Erlang mountainous chickens, were adopted for being infected with MDV. Broilers used in our experiment is special breed for meat production through a long-time high-intensity selection, and it has a higher growth speed in muscle tissue. On the contrary, Erlang mountainous chicken is a native breed, which have not been selected for a long time for any economic trait. After infection with MDV, Erlang mountainous chickens showed more resistance to MDV infection than broilers. It is indicated that overselection for economic trait indeed influence the resistance of chicken response to MDV infection. Previous study showed that the second cytolytic infection induced by MDV occurred in the susceptible chickens from approximately 18
d.p.i onward [29
]. In our experiment, the death of broiler mainly occurred from 16
d.p.i to 21
d.p.i, and we speculated that the death of broilers might be the consequent of MDV-mediated second cytolytic infection during this phase.
Although both genetically susceptible and resistant chickens can be infected with MDV, genetically resistant chickens are capable of controlling the MDV genome load in spleens and feather [26
]. In agreement with this, in the current study, the MDV genome load appeared in spleens of MDV-infected two-breed chickens, and the MDV genome load in spleen of broilers was significantly higher when compared to Erlang mountainous chickens at 4 and 21
d.p.i. These results further indicate that genetic background function as crucial element for affecting MDV genome load in chicken.
It has been proved that RLR-mediated immune pathway mainly is involved in detection and response to RNA virus [35
]. However, little is known about the exact role of RLR-mediated innate immune in vivo
response to DNA virus. Due to the deficiency of RIG-I in chicken, chicken serve as a good animal modern for studying the role of MDA-5 in vivo
response to DNA virus.
In our study, the expression of MDA-5
gene was induced in three immune tissues of two-breed chickens at 4, 7, and 21
d.p.i. It is suggested that MDA-5 might be involved in detection and response against MDV. Because MDV belongs to DNA virus, how does chicken utilize MDA-5 to detect MDV? The study in human primary macrophages found that MDA-5 is responsible for recognition of HSV-1, and the process is dependent on viral replication [36
]. Owing to dsRNA generated by positive-strand RNA viruses and DNA viruses during viral replication [37
], we deduce that dsRNA produced by MDV during replication might serve as resources which are detected byMDA-5 and trigger RLR-mediated immune pathway. Meanwhile, some studies revealed that RNA polymerase III was involved in detection of cytosolic DNA and triggering production of type I in human cell, and inhibition of RNA polymerase III also blocked production of interferon induced by DNA virus, such as Herpes simplex virus-1 (HSV-1) and Epstein-Barr virus (EBV) [38
]. However, the involvement of polymerase III in DNA virus is dependent on RIG-I-mediated immune pathway, independent on MDA-5. Owing to the absence of RIG-I
in chicken, further study is needed to investigate whether chicken polymerase III and MDA-5 coordinately detect MDV and promote the expression of interferon at cell level.
Chicken IRF-3 was firstly identified as the first example of a nonmammalian interferon regulatory factor [41
], but it was thought as the homology of human IRF-7 due to its higher DNA sequence homology with human IRF-7, rather than human IRF-3
]. Mammalian IRF-3 is mainly responsible for induction of IFN-β
gene but not the IFN-α
, yet IRF-7
efficiently activated both IFN-α
]. In our experiment, we found that expression level of IRF-3
was associated with the expression of IFN-α
. It is suggested that chicken IRF-3, like human IRF-7, is also responsible for the expression IFN-α
Previous study indicated that vaccinating with MDV vaccine could enhance the expression of the IRF-3
gene in chicken during latent period of MDV infection [45
]. And the role of interferon chicken response to MDV infection had been proved [24
]. In the present study, we discovered that the expression of both IRF-3
genes had been downregulated in spleen and thymus of broiler at 21
d.p.i, but it showed an upregulation in Erlang mountainous chickens. Owing to the death of broilers observed in this phase, these results further highlight the role of interferon in chicken response against MDV infection. Meanwhile, these results further support the previous conclusion that expression pattern of interferon and cytokine was correlated with genetic background of chicken during MDV infection [26
]. Besides, giving that the MDV-mediated secondly cytolytic replication might be occurred in chicken during this phase, we speculate that the change of these genes expression in broiler is the result of MDV-mediated secondly cytolytic replication which causes immunosuppression in broilers for inhibition of interferon expression. These results further suggest that the downregulation of expression of IRF-3
and interferon gene also might be associated with MDV reactivation. If we could explore deeply the mechanism that MDV infection causes immunosuppression in susceptible chicken, it will make us better understand the interaction between viruses and host.