Innate antiviral responses in porcine nasal mucosal explants inoculated with influenza A virus are comparable with responses in respiratory tissues after viral infection

Starbæk, Sofie M.R.; Andersen, Malene Rask; Brogaard, Louise; Spinelli, Anna; Rapson, Victoria; Glud, Helena Aagaard; Larsen, Lars Erik; Heegaard, Peter M. H.; Nauwynck, Hans; Skovgaard, Kerstin

doi:10.1016/j.imbio.2022.152192

Cited by 8 publications

(5 citation statements)

References 58 publications

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“…ifnc3 overexpression likely limited the replication of PRV-3, preventing further shedding, and heart pathology development. Additionally, cxcl10 is highly expressed in a wide range of tissues following viral infection, including influenza A virus and SARS-CoV-2 (42,43). Expression of cxcl10 is stimulated by IFN and involved in inflammation and chemotaxis of cxcl10 is an important antiviral gene and is highly correlated with viral load in the present study (Table 5).…”

Section: Discussionsupporting

confidence: 50%

“…Expression of cxcl10 is stimulated by IFN and involved in inflammation and chemotaxis of cxcl10 is an important antiviral gene and is highly correlated with viral load in the present study (Table 5). cxcl10 is expressed in a wide range of tissues following viral infection, including influenza A virus and SARS-CoV-2 (42,43). Expression of cxcl10 is stimulated by IFN and involved in inflammation and chemotaxis of lymphocytes including T lymphocytes and NK cells during viral infections.…”

Section: Discussionmentioning

confidence: 99%

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Decreased water temperature enhance Piscine orthoreovirus genotype 3 replication and severe heart pathology in experimentally infected rainbow trout

Sørensen

Cuenca²,

Olsen³

et al. 2023

Front. Vet. Sci.

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Piscine orthoreovirus genotype 3 (PRV-3) was first discovered in Denmark in 2017 in relation to disease outbreaks in rainbow trout (Oncorhynchus mykiss). While the virus appears to be widespread in farmed rainbow trout, disease outbreaks associated with detection of PRV-3 have only occurred in recirculating aquaculture systems, and has predominantly been observed during the winter months. To explore the possible effects of water temperature on PRV-3 infection in rainbow trout, an in vivo cohabitation trial was conducted at 5, 12, and 18°C. For each water temperature, a control tank containing mock-injected shedder fish and a tank with PRV-3 exposed fish were included. Samples were collected from all experimental groups every 2nd week post challenge (WPC) up until trial termination at 12 WPC. PRV-3 RNA load measured in heart tissue of cohabitants peaked at 6 WPC for animals maintained at 12 and 18°C, while it reached its peak at 12 WPC in fish maintained at 5°C. In addition to the time shift, significantly more virus was detected at the peak in fish maintained at 5°C compared to 12 and 18°C. In shedders, fish at 12 and 18°C cleared the infection considerably faster than the fish at 5°C: while shedders at 18 and 12°C had cleared most of the virus at 4 and 6 WPC, respectively, high virus load persisted in the shedders at 5°C until 12 WPC. Furthermore, a significant reduction in the hematocrit levels was observed in the cohabitants at 12°C in correlation with the peak in viremia at 6 WPC; no changes in hematocrit was observed at 18°C, while a non-significant reduction (due to large individual variation) trend was observed at cohabitants held at 5°C. Importantly, isg15 expression was positively correlated with PRV-3 virus load in all PRV-3 exposed groups. Immune gene expression analysis showed a distinct gene profile in PRV-3 exposed fish maintained at 5°C compared to 12 and 18°C. The immune markers mostly differentially expressed in the group at 5°C were important antiviral genes including rigi, ifit5 and rsad2 (viperin). In conclusion, these data show that low water temperature allow for significantly higher PRV-3 replication in rainbow trout, and a tendency for more severe heart pathology development in PRV-3 injected fish. Increased viral replication was mirrored by increased expression of important antiviral genes. Despite no mortality being observed in the experimental trial, the data comply with field observations of clinical disease outbreaks during winter and cold months.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Decreased water temperature enhance Piscine orthoreovirus genotype 3 replication and severe heart pathology in experimentally infected rainbow trout

Sørensen

Cuenca²,

Olsen³

et al. 2023

Front. Vet. Sci.

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“…Synthesis of cDNA was performed in duplicates from a total of 500ng RNA per reaction using QuantiTect Reverse Transcription Kit (Qiagen #205311) as previously described ( 13 ). Non-reverse transcriptase reactions were included as a control for possible genomic DNA contamination.…”

Section: Methodsmentioning

confidence: 99%

“…Fifteen cycles of pre-amplification were performed as previously described ( 13 ) using TaqMan PreAmp Master Mix (Applied Biosystems, PN 4391128), followed by Exonuclease I treatment (New England Biolabs, PN MO293L) of 30 minutes at 37°C and 15 minutes at 80°C.…”

Section: Methodsmentioning

confidence: 99%

Immunogenicity of Bacillus Calmette-Guérin in pigs: potential as a translational model of non-specific effects of BCG

et al. 2023

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BackgroundClinical and immunological studies in humans show that the live attenuated Bacillus Calmette-Guérin (BCG) vaccine has beneficial non-specific effects, increasing resistance against diseases other than tuberculosis. The underlying mechanisms are currently being explored. The pig exhibits considerable physiological similarity to humans in anatomy and physiology, suggesting that similar responses to BCG could be expected. Studies of the non-specific effects of BCG in pigs are scarce. We investigated the feasibility of using pigs as a large animal model to investigate the non-specific immunological effects of BCG.MethodsIn a series of experiments, we randomized newborn or young piglets from conventional farms to receiving BCG or placebo and investigated the persistence of live BCG bacteria in various tissues, the immunogenicity of BCG in ex vivo blood and in vitro stimulation assays, and the acute phase protein and clinical responses to heterologous infectious challenge with influenza A virus or Actinobacillus pleuropneumoniae.ResultsThe BCG vaccine was generally well tolerated. In contrast to humans, no skin reaction in the form of abscesses, ulcers, or scars was observed. Live BCG was recovered from draining lymph nodes in 2/13 animals 20 weeks after vaccination. Specific in vitro responses of IFN-γ to antigen-specific re-stimulation with mycobacterial antigen were increased but not TNF-responses to TLR2 or TLR4 agonists. A few genes were differentially expressed in blood after vaccination, including the antiviral genes RIG-I and CSF1, although the effect disappeared after correction for multiple testing. Clinical symptoms after heterologous bacterial or viral respiratory infections did not differ, nor did virus copies in nasopharyngeal samples after the challenge. However, the acute phase protein response was significantly reduced in BCG-vaccinated animals after influenza challenge but not after A. pleuropneumoniae challenge.DiscussionBCG was safe in pigs, inducing specific immunological responses, but our model did not corroborate the innate immunological responsiveness to BCG seen in humans. The dose of BCG or the bacterial and viral challenges may have been sub-optimal. Even so, the acute phase protein response to influenza infection was significantly reduced in BCG-vaccinated animals.

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“…Cells also express specific PRRs within the cytosolic space, such as Retinoic Acid-Inducible Gene I (RIG-I) and Melanoma Differentiation-Associated Protein 5 (MDA5) [ 47 ], both of which detect dsRNA [ 48 ]. Interestingly, some viruses can be recognized by multiple PRRs due to their replication cycle, which includes phases wherein the virus contains both dsRNA and ssRNA [ 47 , 49 – 52 ]. Thus, the host response to viruses is complex and requires the expression of multiple PRRs by sentinel cells such as monocytes.…”

Section: Introductionmentioning

confidence: 99%

Differential immunophenotype of circulating monocytes from pregnant women in response to viral ligands

Farías-Jofré

Romero

et al. 2023

BMC Pregnancy Childbirth

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Background Viral infections during pregnancy can have deleterious effects on mothers and their offspring. Monocytes participate in the maternal host defense against invading viruses; however, whether pregnancy alters monocyte responses is still under investigation. Herein, we undertook a comprehensive in vitro study of peripheral monocytes to characterize the differences in phenotype and interferon release driven by viral ligands between pregnant and non-pregnant women. Methods Peripheral blood was collected from third-trimester pregnant (n = 20) or non-pregnant (n = 20, controls) women. Peripheral blood mononuclear cells were isolated and exposed to R848 (TLR7/TLR8 agonist), Gardiquimod (TLR7 agonist), Poly(I:C) (HMW) VacciGrade™ (TLR3 agonist), Poly(I:C) (HMW) LyoVec™ (RIG-I/MDA-5 agonist), or ODN2216 (TLR9 agonist) for 24 h. Cells and supernatants were collected for monocyte phenotyping and immunoassays to detect specific interferons, respectively. Results The proportions of classical (CD14hiCD16−), intermediate (CD14hiCD16+), non-classical (CD14loCD16+), and CD14loCD16− monocytes were differentially affected between pregnant and non-pregnant women in response to TLR3 stimulation. The proportions of pregnancy-derived monocytes expressing adhesion molecules (Basigin and PSGL-1) or the chemokine receptors CCR5 and CCR2 were diminished in response to TLR7/TLR8 stimulation, while the proportions of CCR5− monocytes were increased. Such differences were found to be primarily driven by TLR8 signaling, rather than TLR7. Moreover, the proportions of monocytes expressing the chemokine receptor CXCR1 were increased during pregnancy in response to poly(I:C) stimulation through TLR3, but not RIG-I/MDA-5. By contrast, pregnancy-specific changes in the monocyte response to TLR9 stimulation were not observed. Notably, the soluble interferon response to viral stimulation by mononuclear cells was not diminished in pregnancy. Conclusions Our data provide insight into the differential responsiveness of pregnancy-derived monocytes to ssRNA and dsRNA, mainly driven by TLR8 and membrane-bound TLR3, which may help to explain the increased susceptibility of pregnant women to adverse outcomes resulting from viral infection as observed during recent and historic pandemics.

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Innate antiviral responses in porcine nasal mucosal explants inoculated with influenza A virus are comparable with responses in respiratory tissues after viral infection

Cited by 8 publications

References 58 publications

Decreased water temperature enhance Piscine orthoreovirus genotype 3 replication and severe heart pathology in experimentally infected rainbow trout

Decreased water temperature enhance Piscine orthoreovirus genotype 3 replication and severe heart pathology in experimentally infected rainbow trout

Immunogenicity of Bacillus Calmette-Guérin in pigs: potential as a translational model of non-specific effects of BCG

Differential immunophenotype of circulating monocytes from pregnant women in response to viral ligands

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