Coinfection with Haemophilus parasuis serovar 4 increases the virulence of porcine circovirus type 2 in piglets

Liu, Shuqing; Li, Wentao; Wang, Yang; Gu, Changqin; Liu, Xiaoli; Charreyre, Catherine; Fan, Shenxian; He, Qigai

doi:10.1186/s12985-017-0890-6

Cited by 25 publications

(19 citation statements)

References 53 publications

(60 reference statements)

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“…Haemophilus parasuis is the etiological agent of Glässer's disease that causes inflammatory infections such as fibrinous polyserositis, meningitis, arthritis and bronchopneumonia in weaned piglets [1]. As a commensal pathogen in porcine respiratory tract, H. parasuis is frequently associated with porcine reproductive and respiratory syndrome virus, porcine circovirus type 2 and Streptococcus suis infections, resulting in large economic losses in the swine industry worldwide [2,3]. There are currently 15 serotypes of H. parasuis and serotypes 1, 5 and 10 are the most virulent causing rapid death of infected piglets [4,5].…”

Section: Introductionmentioning

confidence: 99%

Epidemiological and PK/PD cutoff values determination and PK/PD-based dose assessment of gamithromycin against Haemophilus parasuis in piglets

Zhou

Liu

et al. 2020

BMC Vet Res

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Background: Gamithromycin is a macrolide approved for the treatment of bovine and swine respiratory diseases. Our study aims to establish the clinical breakpoint and optimum dose regimen for gamithromycin against Haemophilus parasuis in piglets. Results: Gamithromycin was well absorbed and fully bioavailable (87.2-101%) after intramuscular and subcutaneous administrations. The MICs of gamithromycin for 192 clinical H. parasuis isolates ranged from 0.008 to 128 mg/L and the epidemiological cutoff (ECOFF) was calculated as 1.0 mg/L. A large potentiation effect of serum on in vitro susceptibility of gamithromycin was observed for H. parasuis, with broth/serum ratios of 8.93 for MICs and 4.46 for MBCs, respectively. The postantibiotic effects were 1.5 h (1 × MIC) and 2.4 h (4 × MIC), and the postantibiotic sub-MIC effects ranged from 2.7 to 4.3 h. Gamithromycin had rapid and concentration-dependent killing against H. parasuis, and the AUC 24h /MIC ratio correlated well with ex vivo efficacy (R 2 = 0.97). The AUC 24h /MIC targets in serum associated with bacteriostatic, bactericidal and eradication activities were 15.8, 30.3 and 41.2, respectively. The PK/PD-based population dose prediction indicated a probability of target attainment (PTA) for the current marketed dose (6 mg/kg) of 88.9% against H. parasuis. The calculated gamithromycin dose for a PTA ≥ 90% was 6.55 mg/kg. Based on Monte Carlo simulations, the PK/PD cutoff (CO PD) was determined to be 0.25 mg/L. Conclusion: The determined cutoffs and PK/PD-based dose prediction will be of great importance in gamithromycin resistance surveillance and serve as an important step in the establishment of optimum dose regimen and clinical breakpoints.

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Section: Introductionmentioning

confidence: 99%

Epidemiological and PK/PD cutoff values determination and PK/PD-based dose assessment of gamithromycin against Haemophilus parasuis in piglets

Zhou

Liu

et al. 2020

BMC Vet Res

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“…PCVAD is a multifactorial disease that is usually observed co-infection of PCV2 with other pathogens, such as porcine reproductive respiratory syndrome virus (PRRSV), porcine parvovirus (PPV), or haemophilus parasuis ( H. parasuis ), et. al (3, 4). PCV2 infection is required for the occurrence of PCVAD, but PCV2 infection alone rarely produces the full spectrum or severity of clinical disease (5, 6).…”

Section: Introductionmentioning

confidence: 99%

Porcine Circovirus Type 2 Suppresses IL-12p40 Induction via Capsid/gC1qR-Mediated MicroRNAs and Signalings

Wang

et al. 2018

The Journal of Immunology

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Porcine circovirus (PCV) type 2 (PCV2), an immunosuppression pathogen, is often found to increase the risk of other pathogenic infections. Yet the relative immune mechanisms determining the susceptibility of PCV2-infected animals remain unclear. In this study, we confirmed that PCV2 infection suppressed IL-12p40 expression and host Th1 immune response, leading to a weakened pathogenic clearance upon porcine reproductive respiratory syndrome virus (PRRSV) or infection. PCV2 infection suppressed pathogens, LPS/IFN-γ, or LPS/R848-induced IL-12p40 expression in porcine alveolar macrophages. PCV2 capsid (Cap) was the major component to suppress IL-12p40 induction by LPS/IFN-γ, LPS/R848, PRRSV, or Either wild-type PCV2 or mutants PCV2-replicase 1 and PCV type 1-Cap2, which contained PCV2 Cap, significantly decreased IL-12p40 levels and increased the replication of PRRSV and in the lung tissues relative to mock or PCV type 1 infection. gC1qR, a Cap binding protein, was not involved in IL-12p40 induction but mediated the inhibitory effect of PCV2 Cap on IL-12p40 induction. PCV2 also activated PI3K/Akt1 and p38 MAPK signalings to inhibit IL-12p40 expression via inhibition of NF-κB p65 binding to promoter and upregulation of miR-23a and miR-29b. Knockdown of Akt1 and p38 MAPK downregulated miR-23a and miR-29b and increased IL-12p40 expression. Inhibition of miR-23a and miR-29b attenuated the inhibitory effect of PCV2 on IL-12p40 induction, resulting in an increased IL-12p40 expression and Th1 cell population and reduced susceptibility to PRRSV or Taken together, these results demonstrate that PCV2 infection suppresses IL-12p40 expression to lower host Th1 immunity to increase the risk of other pathogenic infection via gC1qR-mediated PI3K/Akt1 and p38 MAPK signaling activation.

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“…Piglets were infected with PCV2 through intranasal (2 mL) and intramuscular (3 mL) inoculation or inoculated with DMEM through the same route. The infective doses and inoculation methods were determined by consulting the literature [22,23]. Blood samples were taken at 0, 5, 8, 11, 14, 17, 21, 24 and 28 days post-inoculation (dpi) with PCV2 for serum isolation.…”

Section: Animal Experimentsmentioning

confidence: 99%

Porcine circovirus type 2 exploits JNK-mediated disruption of tight junctions to facilitate Streptococcus suis translocation across the tracheal epithelium

Wang

Zhou

Lin

et al. 2020

Vet Res

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Porcine circovirus type 2 (PCV2) is considered as the primary pathogen of porcine circovirus-associated disease (PCVAD), which results in significant economic losses worldwide. Clinically, PCV2 often causes disease through coinfection with other bacterial pathogens, including Streptococcus suis (S. suis), and especially the highly prevalent S. suis serotype 2 (SS2). The present study determined that continuous PCV2 infection in piglets down-regulates tight junction proteins (TJ) ZO-1 and occludin in the lungs. Swine tracheal epithelial cells (STEC) were used to explore the mechanisms and consequences of disruption of TJ, and an in vitro tracheal epithelial barrier model was established. Our results show that PCV2 infection in STEC decreases the expression levels of ZO-1 and occludin and increases the permeability of the tracheal epithelial barrier, resulting in easier translocation of SS2. Moreover, Western blot analysis indicates that PCV2 infection activates the JNK/MAPK pathway. The disruption of TJ in SETC and increased permeability of the epithelial barrier induced by PCV2 could be alleviated by inhibition of JNK phosphorylation, which indicates that the JNK/MAPK pathway regulates the expression of ZO-1 and occludin during PCV2 infection. This study allows us to better understand the mechanisms of PCV2 coinfection with bacterial pathogens and provides new insight into controlling the occurrence of PCVAD. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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Coinfection with Haemophilus parasuis serovar 4 increases the virulence of porcine circovirus type 2 in piglets

Cited by 25 publications

References 53 publications

Epidemiological and PK/PD cutoff values determination and PK/PD-based dose assessment of gamithromycin against Haemophilus parasuis in piglets

Epidemiological and PK/PD cutoff values determination and PK/PD-based dose assessment of gamithromycin against Haemophilus parasuis in piglets

Porcine Circovirus Type 2 Suppresses IL-12p40 Induction via Capsid/gC1qR-Mediated MicroRNAs and Signalings

Porcine circovirus type 2 exploits JNK-mediated disruption of tight junctions to facilitate Streptococcus suis translocation across the tracheal epithelium

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