Imbalance between innate antiviral and pro-inflammatory immune responses may contribute to different outcomes involving low- and highly pathogenic avian influenza H5N3 infections in chickens

Abstract

In order to gain further insight into the early virus-host interactions associated with highly pathogenic avian influenza virus infections in chickens, genome-wide expression profiling of chicken lung and brain was carried out at 24 and 72 h post-inoculation (h p.i.). For this purpose two recombinant H5N3 viruses were utilized, each possessing a polybasic HA0 cleavage site but differing in pathogenicity. The original rH5N3 P0 virus, which has a low-pathogenic phenotype, was passaged six times through chickens to give rise to the derivative rH5N3 P6 virus, which is highly pathogenic (Diederich S, Berhane Y, Embury-Hyatt C, Hisanaga T, Handel K et al.J Virol 2015;89:10724-10734). The gene-expression profiles in lung were similar for both viruses, although they varied in magnitude. While both viruses produced systemic infections, differences in clinical disease progression and viral tissue loads, particularly in brain, where loads of rH5N3 P6 were three orders of magnitude higher than rH5N3 P0 at 72 .p.i., were observed. Although genes associated with gene ontology (GO) categories INFα and INFβ biosynthesis, regulation of innate immune response, response to exogenous dsRNA, defence response to virus, positive regulation of NF-κB import into the nucleus and positive regulation of immune response were up-regulated in rH5N3 P0 and rH5N3 P6 brains, fold changes were higher for rH5N3 P6. The additional up-regulation of genes associated with cytokine production, inflammasome and leukocyte activation, and cell-cell adhesion detected in rH5N3 P6 versus rH5N3 P0 brains, suggested that the balance between antiviral and pro-inflammatory innate immune responses leading to acute CNS inflammation might explain the observed differences in pathogenicity.

Transcriptomic analysis of the liver in aged laying hens with different intensity of brown eggshell color

“…In the current study, MX1 expression was upregulated with a log 2 fold change of 3.69 in the DBE group, which is similar to the result for RSAD2. According to Pasick et al [40], the MX1 gene may be involved in the inhibition of influenza A virus replication by preventing primary viral mRNA synthesis in laying hens. We speculate that the up-regulation of MX1 expression in the liver may protect laying hens from viral diseases that are responsible for decreasing intensity of brown eggshell color.…”

Gene expression profiles of the small intestine of village chickens from an Ascaridia galli infested environment

“…The RNA used for qRT-PCR was prepared in the same way as the total RNA extraction and DNase I treatment described above. Five genes were selected based on their functions in the immune response as reported in other chicken studies and significance within the RNA-seq results ( Pasick et al, 2017 , Smith et al, 2015 , Rychlik et al, 2014 ). Primer pairs were designed using Primer3 ( Rozen and Skaletsky, 2000 ) and their primer sequences are listed in Table 1 .…”

Creating Disease Resistant Chickens: A Viable Solution to Avian Influenza?

“…Accordingly, the creation of a transgenic chicken expressing the duck RIG-I has been under patent since 2010 (US20110247091A1). However, it is important to recognise that even in the absence of a RIG-I homologue, chickens still mount a pronounced antiviral response to HPAI virus infections in vivo [ 25 , 26 ]. Indeed, it has been suggested that melanoma differentiation factor (MDA5), a RIG-I like sensor, is able to compensate for the absence of RIG-I in chickens [ 27 ].…”