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Research Project: Intervention Strategies to Control Endemic and New and Emerging Viral Diseases of Swine

Location: Virus and Prion Research

Title: Integrative genomics and network biology in livestock and other domestic animals: differentially expressed miRNAs and tRNA genes affect host homeostasis during highly pathogenic porcine reproductive and respiratory syndrome

item FLEMING, DAMARIUS - Orise Fellow
item Miller, Laura

Submitted to: Frontiers in Genetics
Publication Type: Book / Chapter
Publication Acceptance Date: 7/2/2019
Publication Date: 9/11/2020
Citation: Fleming, D.S., Miller, L.C. 2020. Integrative genomics and network biology in livestock and other domestic animals: differentially expressed miRNAs and tRNA genes affect host homeostasis during highly pathogenic porcine reproductive and respiratory syndrome. Frontiers in Genetics. p. 150.

Interpretive Summary: It is an exciting time for animal bioscience. The ability to apply high-throughput technologies to generate very large data sets in animals is a major leap forward for many species. This Frontiers Research Topic focuses on research work using data-rich technologies specifically in livestock and other domestic animals. In many livestock and domestic species, these high-throughput data types have only recently become available, which gives rise to several unique and interesting computational, analytical and interpretative challenges. Integrative genomics describes experiments that join two or more of these data sets together. One common method to organize and compare these heterogeneous data is in the form of a network, which focuses on the relationships that arise among individual network components. Integrative and network-based approaches have been used extensively in human and model organisms; however, methods and techniques are not always directly translatable to livestock and domestic animals. Unique characteristics of agricultural species can require special consideration in the application and interpretation of integrative and network-based approaches. Furthermore, in many cases, sample collection becomes a limiting factor in experimental design as domestic animal populations can be stratified across the globe and data collection can involve animal sacrifice; therefore, specialized, integrative approaches are necessary to fully leverage existing data sets. A non-coding RNA (ncRNA) is an RNA molecule that is not translated into a protein. Noncoding RNAs belong to several groups and have regulatory roles in cellular processes. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and small RNAs such as microRNAs (miRNAs). For decades, researchers have been exploring the many complications to swine health caused by porcine reproductive and respiratory virus (PRRSV) in order to find ways to reduce losses in commercial pig populations. This chapter describes a study examining the expression profile of miRNA and tRNA expressed in whole blood between healthy and highly pathogenic PRRSV-infected pigs. Overall, the results will serve to bring researchers closer to elucidating how gene function in the pig can become dysregulated due to PRRSV through changes in miRNA and tRNA expression.

Technical Abstract: Background: Porcine respiratory and reproductive syndrome virus (PRRSV) is a singlestranded RNA virus member that infects pigs and causes losses to the commercial industry reaching upward of a billion dollars annually in combined direct and indirect costs. The virus can be separated into etiologies that contain multiple heterologous low and highly pathogenic strains. Recently, the United States has begun to see an increase in heterologous type 2 PRRSV strains of higher virulence (HP-PRRSV). The high pathogenicity of these strains can drastically alter host immune responses and the ability of the animal to maintain homeostasis. Because the loss of host homeostasis can denote underlying changes in gene and regulatory element expression profiles, the study aimed to examine the effect PRRSV infections has on miRNA and tRNA expression and the roles they play in host tolerance or susceptibility. Results: Using transcriptomic analysis of whole blood taken from control and infected pigs at several time points (1, 3, 8 dpi), the analysis returned a total of 149 statistically significant (FDR ' 0.15) miRNAs (n = 89) and tRNAs (n = 60) that were evaluated for possible pro- and anti-viral effects. The tRNA differential expression increased in both magnitude and count as dpi increased, with no statistically significant expression at 1 dpi, but increases at 3 and 8 dpi. The most abundant tRNA amino acid at 3 dpi was alanine, while glycine was the most abundant at 8 dpi. For the miRNAs, focus was put on upregulation that can inhibit gene expression. These results yielded candidates with potential anti- and pro-viral actions such as Ssc-miR-125b, which is predicted to limit PRRSV viral levels, and Ssc-miR-145-5p shown to cause alternative macrophage priming. The results also showed that both the tRNAs and miRNAs displayed expression patterns. Conclusions: The results indicated that the HP-PRRSV infection affects host homeostasis through changes in miRNA and tRNA expression and their subsequent gene interactions that target and influence the function of host immune, metabolic, and structural pathways.