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MicroRNAs in the Host Response to Viral Infections of Veterinary Importance.

ABSTRACT: The discovery of small regulatory non-coding RNAs has been an exciting advance in the field of genomics. MicroRNAs (miRNAs) are endogenous RNA molecules, approximately 22 nucleotides in length, that regulate gene expression, mostly at the posttranscriptional level. MiRNA profiling technologies have made it possible to identify and quantify novel miRNAs and to study their regulation and potential roles in disease pathogenesis. Although miRNAs have been extensively investigated in viral infections of humans, their implications in viral diseases affecting animals of veterinary importance are much less understood. The number of annotated miRNAs in different animal species is growing continuously, and novel roles in regulating host-pathogen interactions are being discovered, for instance, miRNA-mediated augmentation of viral transcription and replication. In this review, we present an overview of synthesis and function of miRNAs and an update on the current state of research on host-encoded miRNAs in the genesis of viral infectious diseases in their natural animal host as well as in selected in vivo and in vitro laboratory models.

SUBMITTER: Samir M

PROVIDER: S-EPMC5065965 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHumans and viruses have co-evolved for millennia resulting in a complex host genetic architecture. Understanding the genetic mechanisms of immune response to viral infection provides insight into disease etiology and therapeutic opportunities.MethodsWe conducted a comprehensive study including genome-wide and transcriptome-wide association analyses to identify genetic loci associated with immunoglobulin G antibody response to 28 antigens for 16 viruses using serological data from 7924 European ancestry participants in the UK Biobank cohort.ResultsSignals in human leukocyte antigen (HLA) class II region dominated the landscape of viral antibody response, with 40 independent loci and 14 independent classical alleles, 7 of which exhibited pleiotropic effects across viral families. We identified specific amino acid (AA) residues that are associated with seroreactivity, the strongest associations presented in a range of AA positions within DRβ1 at positions 11, 13, 71, and 74 for Epstein-Barr virus (EBV), Varicella zoster virus (VZV), human herpesvirus 7, (HHV7), and Merkel cell polyomavirus (MCV). Genome-wide association analyses discovered 7 novel genetic loci outside the HLA associated with viral antibody response (P < 5.0 × 10-8), including FUT2 (19q13.33) for human polyomavirus BK (BKV), STING1 (5q31.2) for MCV, and CXCR5 (11q23.3) and TBKBP1 (17q21.32) for HHV7. Transcriptome-wide association analyses identified 114 genes associated with response to viral infection, 12 outside of the HLA region, including ECSCR: P = 5.0 × 10-15 (MCV), NTN5: P = 1.1 × 10-9 (BKV), and P2RY13: P = 1.1 × 10-8 EBV nuclear antigen. We also demonstrated pleiotropy between viral response genes and complex diseases, from autoimmune disorders to cancer to neurodegenerative and psychiatric conditions.ConclusionsOur study confirms the importance of the HLA region in host response to viral infection and elucidates novel genetic determinants beyond the HLA that contribute to host-virus interaction.

Project description:The purpose of the study was to assess the patterns of global gene expression in peripheral blood cells and uncover the complex dynamics of host response to ARIs such as pandemic H1N1. To understand the molecular bases and network orchestration of host responses, we prospectively enrolled 1610 healthy adults in the fall of 2009 and 2010, followed the subjects with influenza-like illness (N=133) for 3 weeks, and examined changes in their peripheral blood gene expression. We discovered distinct phases of the host response spanning 6 days after infection, and identified genes that differentiate influenza from non-influenza virus infection. We examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. Healthy adults were invited to enroll to be followed for acute respiratory illness (ARI) through two consecutive influenza seasons 2009-2010 and 2010-2011. After subjects provided consent, baseline blood specimens were obtained during enrollment. Subjects were given thermometers and instructions to call and report for evaluation within 48 hours of ARI onset. Those persons who had a new ARI were seen within 48 hours of onset (day 0) and 2, 4, and 6 days later for repeat evaluation, blood specimen collections, and medical care (including the antiviral zanamivir if indicated) and 21 days later for collection of convalescent specimens. Nasal wash samples were collected for virus detection by RT-PCR on day 0 and day 2. Surveillance for influenza was terminated after 5.5 months; all subjects were asked to return for specimen collection and to provide a medical and ARI history in spring of next year. Serum specimens obtained at baseline, day 0 and day 21 visits for illnesses, and the terminal visit were tested simultaneously using hemagglutination-inhibition (HAI) antibody assay for Influenza H1N1, H3N2, and Influenza B strains. Peripheral blood RNA (PaxGene) obtained from blood specimens at each visit were analyzed using Illumina Human HT-12 v4. The study was repeated 2010-2011. A total of 880 arrays, corresponding to 133 individuals, passed quality control and are included in this data set.

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MicroRNAs in the Host Response to Viral Infections of Veterinary Importance.

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