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Identification of Virulence Associated Region during Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus during Attenuation In Vitro: Complex Question with Different Strain Backgrounds.

ABSTRACT: Highly pathogenic porcine reproductive and respiratory syndrome virus PRRSV (HP-PRRSV) was one of the most devastating diseases of the pig industry, among various strategies, vaccination was one of the most useful tools for PRRS control. Attenuated live vaccine was used worldwide, however, the genetic basis of HP-PRRSV virulence change during attenuation remain to be determined. Here, to identify virulence associated regions of HP-PRRSV during attenuation in vitro, six full-length infectious cDNA clones with interchanges of 5'UTR + ORF1a, ORF1b, and ORF2-7 + 3'UTR regions between HP-PRRSV strain HuN4-F5 and its attenuated vaccine strain HuN4-F112 were generated, and chimeric viruses were rescued. Piglets were inoculated with chimeric viruses and their parental viruses, and rectal temperature were recorded daily, and serum were collected for future experiments. Our results showed that ORF1a played an important role on virus replication, cytokine response and lung damage, the exchange of ORF1b and ORF2-7 in different backbone led to different exhibition on virus replication in vivo/vitro and cytokine response. Among 9 PRRSV attenuated series, consistent amino acid changes during PRRSV attenuation were found in NSP4, NSP9, GP2, E, GP3 and GP4. Our study provides a fundamental data for the investigation of PRRSV attenuation, the different results of the virulence change among different studies indicated that different mechanisms might be used during PRRSV virulence enhancement in vivo and attenuation in vitro.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC8780124 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS) and porcine circovirus type 2 (PCV2) is associated with postweaning multisystemic wasting syndrome (PMWS) in pigs. Coinfection with highly pathogenic PRRSV (HP-PRRSV) and PCV2 in the field has recently become extensive in some Asian countries. A synergistic pathogenicity between PRRSV and PCV2 infections has previously been reported. However, the consequences of the sequential infection of pigs with these two viruses are unknown.MethodsThirty 35-day-old piglets were randomly divided into six groups (n = 5 each): HP-PRRSV/PCV2 (group 1, inoculated with HP-PRRSV, then inoculated with PCV2 one week later), PCV2/HP-PRRSV (group 2, inoculated with PCV2, then inoculated with HP-PRRSV one week later), HP-PRRSV+PCV2 (group 3, inoculated with HP-PRRSV and PCV2 concurrently), HP-PRRSV (group 4, inoculated with HP-PRRSV), PCV2 (group 5, inoculated with PCV2), and the control (group 6, uninfected). This experiment lasted 28 days. Clinical symptoms and rectal temperatures were recorded each day after inoculation, body weight was recorded weekly, and serum samples were obtained for viral nucleic acid quantification and antibody titration. Variations in CD3+, CD4+ CD8-, CD3+, CD4-, and CD8+ cells, natural killer (NK) cells, and mononuclear cells were determined by flow cytometry. The serum concentrations of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), and macrophage granulocyte-colony stimulating factor (GM-CSF) were determined. Pathological changes in different tissues from the experimentally infected pigs were recorded.ResultsThe piglets in group 1 had the highest viral loads, the lowest antibody titers, the most-severe clinical signs, and the highest mortality (3/5, 60%; the mortality in the other groups was 0%), and interstitial pneumonia was more severe in this group compare to the other HP-PRRSV infected groups. The serum levels of IFN-γ, TNF-α, IL-10, and GM-CSF varied (increased or decreased) most widely in group 1, as did each immunocyte subgroup.ConclusionsHP-PRRSV infection followed by PCV2 infection enhanced the replication of both viruses in the experimental piglets and led to more-severe clinical signs and lesions, indicating greater synergistic effects during the sequential infection of piglets with HP-PRRSV and then PCV2.

Project description:Background: Porcine respiratory and reproductive syndrome virus (PRRSV) is a single-stranded 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.

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Identification of Virulence Associated Region during Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus during Attenuation In Vitro: Complex Question with Different Strain Backgrounds.

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