Marek’s disease vaccines-induced differential expression of known and novel microRNAs in primary lymphoid organ bursae of White Leghorn

Abstract

Marek's disease (MD) is a contagious disease of domestic chickens caused by MD viruses. MD has been controlled primarily by vaccinations, yet sporadic outbreaks of MD take place worldwide. Commonly used MD vaccines include HVT, SB-1 and CVI988/Rispens and their efficacies are reportedly dependent of multiple factors including host genetics. Our previous studies showed protective efficacy of a MD vaccine can differ drastically from one chicken line to the next. Advanced understanding on the underlying genetic and epigenetic factors that modulate vaccine efficacy would greatly improve the strategy in design and development of more potent vaccines. Two highly inbred lines of White Leghorn were inoculated with HVT and CVI988/Rispens. Bursa samples were taken 26 days post-vaccination and subjected to small RNA sequencing analysis to profile microRNAs (miRNA). A total of 589 and 519 miRNAs was identified in one line, known as line 6 3 , 490 and 630 miRNAs were identified in the other, known as line 7 2 , in response to HVT or CVI988/Rispens inoculation, respectively. HVT and CVI988/Rispens induced mutually exclusive 4 and 13 differentially expressed (DE) miRNAs in line 6 3 birds in contrast to a non-vaccinated group of the same line. HVT failed to induce any DE miRNA and CVI988/Rispens induced a single DE miRNA in line 7 2 birds. Thousands of target genes for the DE miRNAs were predicted, which were enriched in a variety of gene ontology terms and pathways. This finding suggests the epigenetic factor, microRNA, is highly likely involved in modulating vaccine protective efficacy in chicken.

Epigenetic Factor MicroRNAs Likely Mediate Vaccine Protection Efficacy against Lymphomas in Response to Tumor Virus Infection in Chickens through Target Gene Involved Signaling Pathways

“…The highly inbred line 6 3 and line 7 2 chickens used in this study, sharing a common major histocompatibility complex haplotype (B*2), strikingly differ in their ability to convey protective efficacy by up to 40% in response to CVI988/Rispens and up to 82% in response to HVT vaccination against very virulent plus MDV challenge [17,72]. The observed phenotypic differences in the ability to convey protective efficacy in response to vaccination against MDV-induced tumor formation may result from a rather complex mechanistic system potentially involving host genomic and epigenomic variation and vaccine by chicken line interactions [61,73]. This point is well indicated, in turn, by the fact that the MD vaccine's immunologic mechanism of protection remains poorly understood [74].…”

“…The 6 3 and 7 2 lines share a common major histocompatibility complex haplotype (B*2) but differ in susceptibility to avian leukosis virus infection and in resistance to MD [19,59]. Our recent studies revealed that MDV infection induced differential expression of nineteen and nine miRNAs in the two genetic lines of birds, respectively [60], and the MD vaccine HVT and CVI988/Rispens induced differential expression of four and thirteen exclusive microRNAs in the 6 3 line birds, and 0 and one miRNA in the 7 2 line birds, respectively [61]. To advance the fundamental understanding of microRNAs and microRNA expression in association with MDV infection post-vaccination, this study was designed to profile miRNAs and to identify miRNAs with dysregulated expression in the primary lymphoid organ, bursa of Fabricius, in the two genetically divergent inbred lines of chickens in response to a very virulent plus MDV (vv+MDV) challenge post-vaccination.…”

Small RNA deep sequencing revealed microRNAs’ involvement in modulating cellular senescence and immortalization state

“…The small RNA_Seq reads that passed QC were analyzed following the similar procedures described earlier ( Zhang et al., 2020a ). Briefly, the pass-filter ( PF ) reads (the number of clusters that passed Illumina's “Chastity filter”) were analyzed with miRDeep* software package (v3.8) using the default parameters ( An et al., 2013 ) except the adapter sequence and chicken genome-specific index files.…”

RNA2Immune: A Database of Experimentally Supported Data Linking Non-Coding RNA Regulation to the Immune System

“…Vaccines are one of the most significant inventions in improving human health, with great importance being placed on the development of biomarkers that assess the safety and efficacy of vaccine candidates. Altered miRNA expression has been linked to immunological parameters of several infectious diseases after vaccination, such as Marek’s disease [9] , respiratory syncytial virus [10] , and pandemic influenza [11] . Besides infectious diseases, emerging evidence indicates that miRNAs could also influence the effectiveness of cancer vaccines, such as those for breast cancer [12] , colorectal cancer [13] , and melanoma [14] .…”