Cytokine induction by immunostimulatory DNA in porcine PBMC is impaired by a hairpin forming sequence motif from the genome of Porcine Circovirus type 2 (PCV2)

Wikström, Frida Hasslung; Fossum, Caroline; Fuxler, Lisbeth; Kruse, Robert L.; Lövgren, Tanja

doi:10.1016/j.vetimm.2010.09.010

Cited by 23 publications

(9 citation statements)

References 48 publications

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“…PCV2 DNA genome is able to inhibit the production of IFN‐α by stimulated plasmacytoid dendritic cells (Vincent et al, ). Some CpG motifs in the PCV2 genome have been shown to also inhibit the production of IFN‐α by porcine peripheral blood mononuclear cells in vitro (Wikstrom, Fossum, Fuxler, Kruse, & Lovgren, ; Wikstrom et al, ). PCV2 also modulates the expression of another cytokine, the immunosuppressive interleukine 10 (IL‐10) by increasing its production in vitro and in vivo (Darwich et al, , ; Fort et al, ; Kekarainen, Montoya, Mateu, & Segales, ).…”

Section: Introductionmentioning

confidence: 99%

Natural viral co‐infections in pig herds affect hepatitis E virus (HEV) infection dynamics and increase the risk of contaminated livers at slaughter

Salines

Dumarest

Andraud

et al. 2019

Transbound Emerg Dis

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Hepatitis E virus (HEV) is a zoonotic pathogen, in particular genotype 3 HEV is mainly transmitted to humans through the consumption of contaminated pork products. This study aimed at describing HEV infection patterns in pig farms and at assessing the impact of immunomodulating co-infections namely Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Porcine Circovirus Type 2 (PCV2), as well as other individual factors such as piglets' immunity and litters' characteristics on HEV dynamics. A longitudinal follow-up was conducted in three farrow-to-finish farms known to be HEV infected. Overall, 360 piglets were individually monitored from birth to slaughter with regular blood and faecal sampling as well as blood and liver samples collected at slaughterhouse. Virological and serological analyses were performed to detect HEV, PCV2 and PRRSV genome and antibodies. The links between 12 explanatory variables and four outcomes describing HEV dynamics were assessed using cox-proportional hazard models and logistic regression. HEV infection dynamics was found highly variable between farms and in a lower magnitude between batches. HEV positive livers were more likely related to short time-intervals between HEV infection and slaughter time (<40 days, OR = 4.1 [3.7-4.5]). In addition to an influence of piglets' sex and sows' parity, the sequence of co-infections was strongly associated with different HEV dynamics: a PRRSV or PCV2/PRRSV pre-or co-infection was associated with a higher age at HEV shedding (Hazard Ratio = 0.3 [0.2-0.5]), as well as a higher age at HEV seroconversion (HR = 0.5 [0.3-0.9] and HR = 0.4 [0.2-0.7] respectively). A PCV2/PRRSV pre-or co-infection was associated with a longer duration of shedding (HR = 0.5 [0.3-0.8]). Consequently, a PRRSV or PCV2/PRRSV pre-or co-infection was strongly associated with a higher risk of having positive livers at slaughter (OR = 4.1 [1.9-8.9] and OR = 6.5 [3.2-13.2] respectively). In conclusion, co-infections with immunomodulating viruses were found to affect HEV dynamics in the farrow-to-finish pig farms that were followed in this study. K E Y W O R D S hepatitis E virus, infection dynamics, PCV2, PRRSV, public health, risk factors | 1931 SALINES Et AL.

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Section: Introductionmentioning

confidence: 99%

Natural viral co‐infections in pig herds affect hepatitis E virus (HEV) infection dynamics and increase the risk of contaminated livers at slaughter

Salines

Dumarest

Andraud

et al. 2019

Transbound Emerg Dis

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“…While the capacity of single-stranded nucleic acid molecules to fold into higher-order structures is crucial in all living organisms for the correct functioning of tRNA, rRNA, mRNA, and small regulatory RNA molecules, such structures are also particularly important in the biology of many viruses with single-stranded DNA (ssDNA) and single-stranded RNA (ssRNA) genomes. Such structures can play vital roles during the entire viral reproductive cycle, including the initiation of genome replication (6)(7)(8)(9)(10)(11)(12), the regulation of gene expression (13), the control of transcription (14), translation (15)(16)(17), and gene splicing (18), and the modulation of host antiviral responses (19)(20)(21).…”

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confidence: 99%

Evidence of Pervasive Biologically Functional Secondary Structures within the Genomes of Eukaryotic Single-Stranded DNA Viruses

Muhire

Golden

Murrell

et al. 2014

J Virol

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l Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of forming complex secondary structures through Watson-Crick base pairing between their constituent nucleotides. A few of the structural elements formed by such base pairings are, in fact, known to have important functions during the replication of many ssDNA viruses. Unknown, however, are (i) whether numerous additional ssDNA virus genomic structural elements predicted to exist by computational DNA folding methods actually exist and (ii) whether those structures that do exist have any biological relevance. We therefore computationally inferred lists of the most evolutionarily conserved structures within a diverse selection of animal-and plant-infecting ssDNA viruses drawn from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae and analyzed these for evidence of natural selection favoring the maintenance of these structures. While we find evidence that is consistent with purifying selection being stronger at nucleotide sites that are predicted to be base paired than at sites predicted to be unpaired, we also find strong associations between sites that are predicted to pair with one another and site pairs that are apparently coevolving in a complementary fashion. Collectively, these results indicate that natural selection actively preserves much of the pervasive secondary structure that is evident within eukaryote-infecting ssDNA virus genomes and, therefore, that much of this structure is biologically functional. Lastly, we provide examples of various highly conserved but completely uncharacterized structural elements that likely have important functions within some of the ssDNA virus genomes analyzed here.

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“…First, we confirm that IFN- α was mostly secreted by pDCs but not by other cells from PBMCs after CpG2216 stimulation (Supplemental Figure 1 ). Also, as shown in Supplemental Figure 2 , CpG ODN 2216, but not control ODN, was able to provoke the synthesis of IFN- α ; meanwhile, two reported inhibitory ODNs [ 45 – 47 ] of TLR9 suppressed CpG2216-mediated IFN- α secretion to less than 50% (Supplemental Figure 2 ).…”

Section: Resultsmentioning

confidence: 92%

Increased Abundance of Plasmacytoid Dendritic Cells and Interferon-Alpha Induces Plasma Cell Differentiation in Patients of IgA Nephropathy

Zheng

Wang

Fan

et al. 2017

Mediators of Inflammation

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The roles of pDC and IFN-α have not been well defined in IgA nephropathy (IgAN). In this study, we investigated the abundance of pDCs and IFN-α in IgAN patients and the response of peripheral blood mononuclear cells (PBMCs) after stimulation of the pDC-preferred TLR9 ligand CpG2216. The effects of IFN-α on plasma cell differentiation and leukocyte migration were also investigated. Here, we found that the percentages of pDCs were increased in PBMCs of IgAN patients, than in those of healthy controls. Plasma levels of IFN-α proteins and abundance of plasma cells were higher in IgAN patients than in healthy donors. Plasma IFN-α levels were positively associated with proteinuria, renal IgM deposition, and renal tubular atrophy/interstitial fibrosis grade in IgAN patients. Ex vivo activation of TLR9 on pDCs resulted in increased IFN-α production and enhanced plasma cell differentiation in IgAN patients as compared with healthy donors. IFN-α treatment led to increased plasma cell differentiation in vitro. IFN-α also significantly promoted expression of chemokines IP-10 and MCP-1 in human mesangial cells, which subsequently facilitated the transendothelial migration of human CD4+ and CD14+ cells. In conclusion, pDC and its secreted cytokine IFN-α may play important roles in pathological changes of IgA nephropathy.

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Cytokine induction by immunostimulatory DNA in porcine PBMC is impaired by a hairpin forming sequence motif from the genome of Porcine Circovirus type 2 (PCV2)

Cited by 23 publications

References 48 publications

Natural viral co‐infections in pig herds affect hepatitis E virus (HEV) infection dynamics and increase the risk of contaminated livers at slaughter

Natural viral co‐infections in pig herds affect hepatitis E virus (HEV) infection dynamics and increase the risk of contaminated livers at slaughter

Evidence of Pervasive Biologically Functional Secondary Structures within the Genomes of Eukaryotic Single-Stranded DNA Viruses

Increased Abundance of Plasmacytoid Dendritic Cells and Interferon-Alpha Induces Plasma Cell Differentiation in Patients of IgA Nephropathy

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