Structure-Dependent Modulation of Alpha Interferon Production by Porcine Circovirus 2 Oligodeoxyribonucleotide and CpG DNAs in Porcine Peripheral Blood Mononuclear Cells

Wikström, Frida Hasslung; Meehan, Brian; Berg, Mikael; Timmusk, Salme; Elving, Josefine; Fuxler, Lisbeth; Magnusson, Mattias; Allan, Gordon; McNeilly, F.; Fossum, Caroline

doi:10.1128/jvi.02797-06

Cited by 44 publications

(22 citation statements)

References 46 publications

(62 reference statements)

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“…Indeed, the ability to counter IFN-a-mediated responses through different pathways, and thereby interfere with the immune mechanisms of the host, has been reported for several viruses (Garcia-Sastre and Biron, 2006). In the case of PCV2, recent studies showed that PCV2 or PCV2-CpG motifs may inhibit or induce IFN-a responses (Vincent et al, 2005;Wikstrom et al, 2007) depending on the cell subset studied and on the structure of CpGs. Vincent et al (2007) reported that PCV2 was able to block IFN-a induction in NIPCs, suggesting the inmunomodulatory activity of PCV2 as a key event in the pathogenesis of PMWS.…”

Section: Discussionmentioning

confidence: 99%

Development of cell-mediated immunity to porcine circovirus type 2 (PCV2) in caesarean-derived, colostrum-deprived piglets

Fort

Fernandes

Nofrarías

et al. 2009

Veterinary Immunology and Immunopathology

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The interaction between porcine circovirus type 2 (PCV2) and the pig immune system has been suggested to be a determinant event for the pathogenesis of postweaning multisystemic wasting syndrome (PMWS). To gain insight into the host immune mechanisms developed upon PCV2 infection, early innate and adaptive immune responses were examined in 1-week-old, caesarean-derived, colostrum-deprived piglets using a subclinical infection model of PCV2 in combination with lipopolysaccharide (LPS) as a potential immunostimulation factor. The use of LPS did not show any significant effect on the course of PCV2 infection, nor did in the evolution of the immunological parameters evaluated. Ex vivo responses were detected as early as 1 day post-infection (PI) and consisted of an elevation of the plasmatic levels of interleukin (IL)-8 in PCV2-inoculated pigs followed by an increase on plasmatic IFN-alpha at day 5 PI. Regarding IL-10, only one PCV2-inoculated pig was positive (day 7 PI); this pig was the only one in which viremia persisted until the end of the study. In vitro cytokine determination showed that, regardless of the treatment administrated to the pigs, an IL-10 release was observed when peripheral blood mononuclear cells (PBMC) cultures were stimulated with PCV2. Seroconvertion to PCV2 measured by an immunoperoxidase monolayer assay (IPMA) occurred between 7 and 14 days PI, whereas neutralizing antibodies (NA) did not appear until day 29 PI. PCV2 DNA was first detected in serum at day 7 PI, reaching the peak of viremia between days 14 and 21 PI, followed by a drop in viral load that was found coincident with the appearance of PCV2-specific IFN-gamma-secreting cells (PCV2-IFN-gamma-SC) and NA. Results from the present work suggest that viral clearance might be mediated by the development of PCV2-IFN-gamma-SC in contribution to the PCV2-specific NA.

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Section: Discussionmentioning

confidence: 99%

Development of cell-mediated immunity to porcine circovirus type 2 (PCV2) in caesarean-derived, colostrum-deprived piglets

Fort

Fernandes

Nofrarías

et al. 2009

Veterinary Immunology and Immunopathology

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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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“…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).…”

mentioning

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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Structure-Dependent Modulation of Alpha Interferon Production by Porcine Circovirus 2 Oligodeoxyribonucleotide and CpG DNAs in Porcine Peripheral Blood Mononuclear Cells

Cited by 44 publications

References 46 publications

Development of cell-mediated immunity to porcine circovirus type 2 (PCV2) in caesarean-derived, colostrum-deprived piglets

Development of cell-mediated immunity to porcine circovirus type 2 (PCV2) in caesarean-derived, colostrum-deprived piglets

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

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