scholarly journals Efficacy of a live attenuated highly pathogenic PRRSV vaccine against a NADC30-like strain challenge: implications for ADE of PRRSV

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Xin-xin Chen ◽  
Xinyu Zhou ◽  
Tengda Guo ◽  
Songlin Qiao ◽  
Zhenhua Guo ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Molecular Mechanisms ◽  
Clinical Signs ◽  
Bodyweight Gain ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Experimental Conditions ◽  
Highly Pathogenic ◽  
Highly Pathogenic Prrsv

Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) infection can cause severe reproductive failure in sows and respiratory distress in pigs of all ages, leading to major economic losses. To date, there are still no effective strategies to prevent and control PRRSV. Antibody-dependent enhancement (ADE), a phenomenon in which preexisting non-neutralizing antibodies or sub-neutralizing antibodies facilitate virus entry and replication, may be a significant obstacle in the development of effective vaccines for many viruses, including PRRSV. However, the contribution of ADE to PRRSV infection remains controversial, especially in vivo. Whether attenuated PRRSV vaccines prevent or worsen subsequent disease in pigs infected by novel PRRSV strains requires more research. In the present study, in vivo experiments were conducted to evaluate ADE under different immune statuses, which were produced by waiting different lengths of time after vaccination with a commercially available attenuated highly pathogenic PRRSV (HP-PRRSV) vaccine (JXA1-R) before challenging the pigs with a novel heterologous NADC30-like strain. Results Piglets that were vaccinated before being challenged with PRRSV exhibited lower mortality rates, lower body temperatures, higher bodyweight gain, and lower viremia. These results demonstrate that vaccination with JXA1-R alleviated the clinical signs of PRRSV infection in all vaccinated groups. Conclusions The obtained data indicate that the attenuated vaccine test here provided partial protection against the NADC30-like strain HNhx. No signs of enhanced PRRSV infection were observed under the applied experimental conditions. Our results provide some insight into the molecular mechanisms underlying vaccine-induced protection or enhancement in PRRSV.

scholarly journals Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Induces Interleukin-17 Production via Activation of the IRAK1-PI3K-p38MAPK-C/EBPβ/CREB Pathways

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Honglei Wang ◽  
Li Du ◽  
Fang Liu ◽  
Zeyu Wei ◽  
Li Gao ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Molecular Mechanisms ◽  
Nonstructural Protein ◽  
Severe Pneumonia ◽  
Pi3k Inhibitor ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Binding Motif ◽  
Interleukin 17 ◽  
Highly Pathogenic

ABSTRACT Porcine reproductive and respiratory syndrome virus (PRRSV) is widely prevalent in pigs, resulting in significant economic losses worldwide. A compelling impact of PRRSV infection is severe pneumonia. In the present study, we found that interleukin-17 (IL-17) was upregulated by PRRSV infection. Subsequently, we demonstrated that PI3K and p38MAPK signaling pathways were essential for PRRSV-induced IL-17 production as addition of phosphatidylinositol 3-kinase (PI3K) and p38MAPK inhibitors dramatically reduced IL-17 production. Furthermore, we show here that deleting the C/EBPβ and CREB binding motif in porcine IL-17 promoter abrogated its activation and that knockdown of C/EBPβ and CREB remarkably impaired PRRSV-induced IL-17 production, suggesting that IL-17 expression was dependent on C/EBPβ and CREB. More specifically, we demonstrate that PRRSV nonstructural protein 11 (nsp11) induced IL-17 production, which was also dependent on PI3K-p38MAPK-C/EBPβ/CREB pathways. We then show that Ser74 and Phe76 amino acids were essential for nsp11 to induce IL-17 production and viral rescue. In addition, IRAK1 was required for nsp11 to activate PI3K and enhance IL-17 expression by interacting with each other. Importantly, we demonstrate that PI3K inhibitor significantly suppressed IL-17 production and lung inflammation caused by HP-PRRSV in vivo, implicating that higher IL-17 level induced by HP-PRRSV might be associated with severe lung inflammation. These findings provide new insights onto the molecular mechanisms of the PRRSV-induced IL-17 production and help us further understand the pathogenesis of PRRSV infection. IMPORTANCE Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) associated with severe pneumonia has been one of the most important viral pathogens in pigs. IL-17 is a proinflammatory cytokine that might be associated with the strong inflammation caused by PRRSV. Therefore, we sought to determine whether PRRSV infection affects IL-17 expression, and if so, determine this might partially explain the underlying mechanisms for the strong inflammation in HP-PRRSV-infected pigs, especially in lungs. Here, we show that PRRSV significantly induced IL-17 expression, and we subsequently dissected the molecular mechanisms about how PRRSV regulated IL-17 production. Furthermore, we show that Ser74 and Phe76 in nsp11 were indispensable for IL-17 production and viral replication. Importantly, we demonstrated that PI3K inhibitor impaired IL-17 production and alleviated lung inflammation caused by HP-PRRSV infection. Our findings will help us for a better understanding of PRRSV pathogenesis.

scholarly journals A novel fiber-2-edited live attenuated vaccine candidate against the highly pathogenic serotype 4 fowl adenovirus

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Quan Xie ◽  
Shiya Cao ◽  
Wei Zhang ◽  
Weikang Wang ◽  
Luyuan Li ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Insertion Site ◽  
Clinical Signs ◽  
Economic Losses ◽  
Lethal Challenge ◽  
Highly Pathogenic ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Fowl Adenovirus

AbstractRecently, the outbreaks of hydropericardium-hepatitis syndrome (HHS) caused by the highly pathogenic fowl adenovirus serotype 4 (FAdV-4) have resulted in huge economic losses to the poultry industry globally. Although several inactivated or subunit vaccines have been developed against FAdV-4, live-attenuated vaccines for FAdV-4 are rarely reported. In this study, a recombinant virus FA4-EGFP expressing EGFP-Fiber-2 fusion protein was generated by the CRISPR/Cas9 technique. Although FA4-EGFP shows slightly lower replication ability than the wild type (WT) FAdV-4, FA4-EGFP was significantly attenuated in vivo compared with the WT FAdV-4. Chickens infected with FA4-EGFP did not show any clinical signs, and all survived to 14 day post-infection (dpi), whereas those infected with FAdV-4 showed severe clinical signs with HHS and all died at 4 dpi. Besides, the inoculation of FA4-EGFP in chickens provided efficient protection against lethal challenge with FAdV-4. Compared with an inactivated vaccine, FA4-EGFP induced neutralizing antibodies with higher titers earlier. All these data not only provide a live-attenuated vaccine candidate against the highly pathogenic FAdV-4 but also give a potential insertion site for developing FAdV-4-based vaccine vectors for delivering foreign antigens.

scholarly journals The Function of the PRRSV–Host Interactions and Their Effects on Viral Replication and Propagation in Antiviral Strategies

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 364
Author(s):  
Jun Ma ◽  
Lulu Ma ◽  
Meiting Yang ◽  
Wei Wu ◽  
Wenhai Feng ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Rna Virus ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Live Virus ◽  
Virus Challenge ◽  
Host Interactions

Porcine reproductive and respiratory syndrome virus (PRRSV) affects the global swine industry and causes disastrous economic losses each year. The genome of PRRSV is an enveloped single-stranded positive-sense RNA of approximately 15 kb. The PRRSV replicates primarily in alveolar macrophages of pig lungs and lymphatic organs and causes reproductive problems in sows and respiratory symptoms in piglets. To date, studies on how PRRSV survives in the host, the host immune response against viral infections, and pathogenesis, have been reported. PRRSV vaccines have been developed, including inactive virus, modified live virus, attenuated live vaccine, DNA vaccine, and immune adjuvant vaccines. However, there are certain problems with the durability and effectiveness of the licensed vaccines. Moreover, the high variability and fast-evolving populations of this RNA virus challenge the design of PRRSV vaccines, and thus effective vaccines against PRRSV have not been developed successfully. As is well known, viruses interact with the host to escape the host’s immune response and then replicate and propagate in the host, which is the key to virus survival. Here, we review the complex network and the mechanism of PRRSV–host interactions in the processes of virus infection. It is critical to develop novel antiviral strategies against PRRSV by studying these host–virus interactions and structures to better understand the molecular mechanisms of PRRSV immune escape.

Potential Health Benefits Of A Pomegranate Extract, Rich In Phenolic Compounds, In Intestinal Inflammation

2021 ◽  
Vol 17 ◽  
Author(s):  
Marco Raffaele ◽  
Khaled Greish ◽  
Luca Vanella ◽  
Giuseppe Carota ◽  
Fatemah Bahman ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Inflammatory Marker ◽  
Experimental Models ◽  
Cellular Damage ◽  
Experimental Conditions ◽  
Potential Health

Background: Pomegranate is a fruit rich in bioactive compounds such as punicalagins, gallic acid, and ellagic acid derivatives. It has been widely used since ancient times in traditional medicine for a wide variety of diseases. It has been reported that bioactive compounds, such as polyphenols, are able to induce the expression of cytoprotective enzymes, including HO-1. The contribution of HO-1 activity to the prevention of intestinal inflammation has been shown in different models of Inflammatory bowel diseases (IBD). Objective: Aim of the present research was to investigate the molecular mechanisms involved in the beneficial effects of a pomegranate extract (PE), rich in bioactive compounds in intestinal inflammation. Methods: Caco-2 cells exposed to LPS and DSS induced colitis were chosen as convenient experimental models of intestinal inflammation. Results: Results obtained in our experimental conditions, showed that PE in vitro was able to induce HO-1 and to reduce cellular damage and oxidative stress through increase of GSH levels. Moreover, PE was able to decrease the pro-inflammatory marker IL-8 levels and to activate TIGAR pathway. The results obtained in vivo, in agreement with the data obtained in vitro, highlighted the ability of PE to reduce intestinal inflammation, preserve the colon length and histological features and reduce IL-6 levels compared to the DSS treated group. Conclusion: PE, rich in bioactive compounds, could contribute, as supportive therapy, to enhance the effects of the conventional therapeutic strategies to the management of IBD.

scholarly journals Genomic Analysis of a Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Circulating in Pig Farms in West China

2018 ◽  
Vol 6 (27) ◽  
Author(s):  
Chenyu Zhang ◽  
Hu Shan ◽  
Jianxin Wen
Keyword(s):  
Genomic Analysis ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Highly Pathogenic ◽  
West China ◽  
Pig Farms ◽  
Long Time

Porcine reproductive and respiratory syndrome virus (PRRSV), which leads to tremendous economic losses worldwide, is currently one of the most threatening viruses for the swine industry. However, PRRSV outbreaks in West China are rarely reported, even though the virus has remained active for a long time across the country.

scholarly journals Anti-Inflammatory and Antinociceptive Activities of Anthraquinone-2-Carboxylic Acid

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Jae Gwang Park ◽  
Seung Cheol Kim ◽  
Yun Hwan Kim ◽  
Woo Seok Yang ◽  
Yong Kim ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Molecular Mechanisms ◽  
Interleukin 1 ◽  
Nuclear Factor ◽  
Experimental Conditions ◽  
Gene Assay ◽  
Anti Inflammatory ◽  
Gastric Irritation

Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, thein vivoanti-inflammatory activity and molecular mechanisms of anthraquinones have not been fully elucidated. We investigated the activity of anthraquinones using acute inflammatory and nociceptive experimental conditions. Anthraquinone-2-carboxylic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA), one of the major anthraquinones identified from Brazilian taheebo, ameliorated various inflammatory and algesic symptoms in EtOH/HCl- and acetylsalicylic acid- (ASA-) induced gastritis, arachidonic acid-induced edema, and acetic acid-induced abdominal writhing without displaying toxic profiles in body and organ weight, gastric irritation, or serum parameters. In addition, AQCA suppressed the expression of inflammatory genes such as cyclooxygenase- (COX-) 2 in stomach tissues and lipopolysaccharide- (LPS-) treated RAW264.7 cells. According to reporter gene assay and immunoblotting analyses, AQCA inhibited activation of the nuclear factor- (NF-)κB and activator protein- (AP-) 1 pathways by suppression of upstream signaling involving interleukin-1 receptor-associated kinase 4 (IRAK1), p38, Src, and spleen tyrosine kinase (Syk). Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive componentsin vivo, thus contributing to the immune regulatory role of fruits and herbs.

scholarly journals GP5 Protein-based ELISA for the Detection of PRRSV Antibodies

2016 ◽  
Vol 19 (3) ◽  
pp. 495-501 ◽  
Author(s):  
Y. Wang ◽  
J. Guo ◽  
S. Qiao ◽  
Q. Li ◽  
J. Yang ◽  
...  
Keyword(s):  
Cell Culture ◽  
Western Blot ◽  
Neutralizing Antibodies ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Flask Culture ◽  
E Coli ◽  
Swine Pathogen ◽  
And Control ◽  
Glycoprotein 5

AbstractPorcine reproductive and respiratory syndrome virus (PRRSV) is an important swine pathogen, causing huge economic losses each year worldwide. Immunization with vaccines containing the glycoprotein 5 (GP5) of PRRSV is the main measure to induce neutralizing antibodies and control the disease. Here, we developed a GP5 protein-based ELISA for detecting antibodies against PRRSV. The overall yield of purified GP5 inE. coliflask culture was more than 45 mg/L cell culture. Western blot and IFA indicated that the GP5 protein was highly immunogenic. After optimization and validation with IDEXX PRRS using 566 clinical sera, the DSN, DSP, and accuracy of GP5-ELISA were 81.39%, 75.96%, and 80.39%, respectively. Besides, GP5-ELISA is highly specific, showing no cross-reactions with sera against other important swine pathogens. Hence, GP5 is a good diagnostic antigen and the GP5 protein-based ELISA has the potential to be used in the field.

scholarly journals Evaluation of Four Commercial Vaccines for the Protection of Piglets against the Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus (hp-PRRSV) QH-08 Strain

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1020
Author(s):  
Yaozhong Ding ◽  
Ashenafi Kiros Wubshet ◽  
Xiaolong Ding ◽  
Zhongwang Zhang ◽  
Qian Li ◽  
...  
Keyword(s):  
Genetic Distance ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Prevention Strategies ◽  
Complete Protection ◽  
Highly Pathogenic ◽  
Partial Protection ◽  
Live Vaccines ◽  
Control And Prevention ◽  
Group 5

Vaccination is the best way to prevent economic losses from highly pathogenic porcine reproductive and respiratory syndrome virus (hp-PRRSV) disease. However, the commercially available vaccines need to periodically evaluate their efficacy against infections caused by new hp-PRRSV variants. Therefore, the objective of this study was to evaluate the efficacy of four (two modified live vaccines (MLV) and two inactivated) PRRSV commercial vaccines in piglets challenged with QH-08 and to estimate the genetic distance of the vaccine strains from recently isolated (QH-08) filed strain. Randomly, piglets (n = 5) allocated in groups 1–4 were immunized with Ingelvac PRRS MLV, CH-1a, JXA1, and JXA1-RMLV vaccines, whereas the infected and non-infected control piglets in groups 5 and 6 (n = 3), respectively, were subjected to PBS. Results indicated that JXA1 and JXA1-R MLV vaccines showed complete protection, but Ingelvac PRRS MLV and CH-1α vaccines revealed partial protection against the QH-08 PRRSV challenge. Similarly, vaccinated and challenged pigs showed lower macroscopic and microscopic lesions than the pigs in group 5. Our findings demonstrated a new insight that the variation in ORF1a and 1b coding sequence could significantly affect PRRSV vaccines efficacy. In conclusion, QH-08 is a good candidate for the design and development of an innovative PRRSV vaccine that ultimately helps in the control and prevention strategies.

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