Interferon alpha inhibits replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine

Brockmeier, Susan L.; Loving, Crystal L.; Eberle, Kirsten C.; Hau, Samantha J.; Buckley, Alexandra; Geelen, Albert Van; Montiel, Nestor A.; Nicholson, Tracy L.; Lager, Kelly M.

doi:10.1016/j.vetmic.2017.11.004

Cited by 23 publications

(20 citation statements)

References 15 publications

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“…The vaccine strain was titrated, but no problem was detected. As IFNa was recently shown to strongly inhibit the replication of a genotype 2 PRRS MLV [21], we hypothesized this cytokine could be responsible for the inhibition of vaccine replication in our AÀV+ piglets. Indeed, the levels of IFNa detected in piglets from the present study at 3 woa were much higher than those from our previous study [14] and in the same range as the concentration shown to be able to completely inhibit PRRS MLV replication [22].…”

Section: Discussionmentioning

confidence: 98%

Maternally-derived neutralizing antibodies reduce vaccine efficacy against porcine reproductive and respiratory syndrome virus infection

Renson

Fablet

Andraud

et al. 2019

Vaccine

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a b s t r a c tModified live virus (MLV) vaccines are commonly used to reduce the impact of porcine reproductive and respiratory syndrome (PRRS) but limited efficacy is achieved in field conditions. Here, we evaluated the impact of maternally-derived neutralizing antibodies (MDNAs) on vaccine efficacy after PRRS virus (PRRSV) challenge. Piglets with low (AÀ) or high (A+) MDNA levels derived from a commercial pig herd were moved to experimental facilities to be vaccinated (V+) or not (VÀ) with a PRRSV-1 MLV vaccine at 3 weeks of age (woa). Because of unexpectedly low vaccine detection in AÀV+ piglets post-vaccination (pv), all V+ piglets received a second vaccination at 4 woa. Five weeks (W5) pv, piglets were inoculated with a PRRSV-1 field strain to evaluate vaccine protection, and were mingled 24 h later with noninoculated piglets of similar immune status to assess viral transmission. Vaccine strain was detected at W2 pv in 69% and 6% of AÀV+ and A+V+ piglets, and at W5 pv in 50% and 25% of AÀV+ and A+V+ piglets, respectively. At W5 pv, 94% of AÀV+ and 44% of A+V+ piglets seroconverted, with a significant IFNg response induction in the AÀV+ group only. After challenge, compared to the VÀ inoculated group, viremia was 100-fold lower at 10 days post-infection in AÀV+ whereas viremia was not significantly reduced in A+V+ piglets. A lower transmission rate was estimated for the AÀV+ group: 0.15 [0.07-0.29] versus 0.44 [0.18-1.76] and 0.32 [0.14-0.68] for the A+V+ and VÀ groups, respectively. Investigations about the low vaccine strain detection after the first vaccination suggested a relationship between IFNa levels and vaccine strain detection in AÀV+ piglets. We showed that MDNAs impair vaccine efficacy against PRRSV both in inoculated and contact piglets, probably by reducing vaccine replication. IFNa may also interfere with PRRSV vaccination. These new data could help improving vaccination protocols.

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Section: Discussionmentioning

confidence: 98%

Maternally-derived neutralizing antibodies reduce vaccine efficacy against porcine reproductive and respiratory syndrome virus infection

Renson

Fablet

Andraud

et al. 2019

Vaccine

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“…To successfully fight against PRRSV infection, macrophages have evolved various strategies to regulate antiviral responses, such as regulating the production of IFN-α/β [17]. The previous evidence suggested that PRRSV was susceptible to IFNs [18], whereas PRRSV-mediated suppression of IFNs production helped the virus circumvent the host antiviral responses [19]. Besides, the pro-inflammatory cytokines including IL-1, IL-6, IL-8, and TNF-α mainly produced in PAMs after virus invasion, play critical roles in infection and pathogenesis of PRRSV [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Unveiling the long non-coding RNA profile of porcine reproductive and respiratory syndrome virus-infected porcine alveolar macrophages

Gao

Pan

et al. 2021

BMC Genomics

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Background Long noncoding RNA (lncRNA) is highly associated with inflammatory response and virus-induced interferon production. By far the majority of studies have focused on the immune-related lncRNAs of mice and humans, but the function of lncRNAs in porcine immune cells are poorly understood. Porcine reproductive and respiratory syndrome virus (PRRSV) impairs local immune responses in the lungs of nursery and growing pigs, whereas the virus triggers the inflammatory responses. Porcine alveolar macrophage (PAM) is the primary target cell of PRRSV, thus PRRSV is used as an in vitro model of inflammation. Here, we profiled lncRNA and mRNA repertories from PRRSV-infected PAMs to explore the underlying mechanism of porcine lncRNAs in regulating host immune responses. Results In this study, a total of 350 annotated lncRNAs and 1792 novel lncRNAs in PAMs were identified through RNA-seq analysis. Among them 86 differentially expressed (DE) lncRNAs and 406 DE protein-coding mRNAs were identified upon PRRSV incubation. GO category and KEGG pathway enrichment analyses revealed that these DE lncRNAs and mRNAs were mainly involved in inflammation- and pathogen infection-induced pathways. The results of dynamic correlated expression networks between lncRNAs and their predicted target genes uncovered that numerous lncRNAs, such as XLOC-022175, XLOC-019295, and XLOC-017089, were correlated with innate immune genes. Further analysis validated that these three lncRNAs were positively correlated with their predicted target genes including CXCL2, IFI6, and CD163. This study suggests that porcine lncRNAs affect immune responses against PRRSV infection through regulating their target genes in PAMs. Conclusion This study provides both transcriptomic and epigenetic status of porcine macrophages. In response to PRRSV infection, comprehensive DE lncRNAs and mRNAs were profiled from PAMs. Co-expression analysis demonstrated that lncRNAs are emerging as the important modulators of immune gene activities through their critical influence upon PRRSV infection in porcine macrophages.

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“…However, with PRRSV infection, such response is weakened or significantly suppressed. Some authors have stated that the expression of IFN –α inhibits the replication of viruses, including PRRSV in vitro ( Albina et al, 1998 ; Zhang et al, 2014 ; Brockmeier et al, 2017 ). The expression of inflammatory cytokine plays a very significant role in the organization of the host immune system against a variety of viral infection ( Brockmeier et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

“…Some authors have stated that the expression of IFN –α inhibits the replication of viruses, including PRRSV in vitro ( Albina et al, 1998 ; Zhang et al, 2014 ; Brockmeier et al, 2017 ). The expression of inflammatory cytokine plays a very significant role in the organization of the host immune system against a variety of viral infection ( Brockmeier et al, 2017 ). TNF, IL-1β, and IL-6 are essential activators of the nuclear transcription factor, NF-κB ( Christman et al, 2000 ; Mori et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Antiviral Strategies of Chinese Herbal Medicine Against PRRSV Infection

et al. 2020

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Bioactive compounds from Traditional Chinese Medicines (TCMs) are gradually becoming an effective alternative in the control of porcine reproductive and respiratory syndrome virus (PRRSV) because most of the commercially available PRRSV vaccines cannot provide full protection against the genetically diverse strains isolated from farms. Besides, the incomplete attenuation procedure involved in the production of modified live vaccines (MLV) may cause them to revert to the more virulence forms. TCMs have shown some promising potentials in bridging this gap. Several investigations have revealed that herbal extracts from TCMs contain molecules with significant antiviral activities against the various stages of the life cycle of PRRSV, and they do this through different mechanisms. They either block PRRSV attachment and entry into cells or inhibits the replication of viral RNA or viral particles assembly and release or act as immunomodulators and pathogenic pathway inhibitors through cytokines regulations. Here, we summarized the various antiviral strategies employed by some TCMs against the different stages of the life cycle of PRRSV under two major classes, including direct-acting antivirals (DAAs) and indirect-acting antivirals (IAAs). We highlighted their mechanisms of action. In conclusion, we recommended that in making plans for the use of TCMs to control PRRSV, the pathway forward must be built on a real understanding of the mechanisms by which bioactive compounds exert their effects. This will provide a template that will guide the focus of collaborative studies among researchers in the areas of bioinformatics, chemistry, and proteomics. Furthermore, available data and procedures to support the efficacy, safety, and quality control levels of TCMs should be well documented without any breach of data integrity and good manufacturing practices.

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Interferon alpha inhibits replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine

Cited by 23 publications

References 15 publications

Maternally-derived neutralizing antibodies reduce vaccine efficacy against porcine reproductive and respiratory syndrome virus infection

Maternally-derived neutralizing antibodies reduce vaccine efficacy against porcine reproductive and respiratory syndrome virus infection

Unveiling the long non-coding RNA profile of porcine reproductive and respiratory syndrome virus-infected porcine alveolar macrophages

Antiviral Strategies of Chinese Herbal Medicine Against PRRSV Infection

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