scholarly journals Major Vault Protein Inhibits Porcine Reproductive and Respiratory Syndrome Virus Infection in CRL2843CD163 Cell Lines and Primary Porcine Alveolar Macrophages

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2267
Author(s):  
Xiaoping Wu ◽  
Junyang Fang ◽  
Qiuping Huang ◽  
Xu Chen ◽  
Zhongyi Guo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Alveolar Macrophages ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Major Vault Protein ◽  
Swine Industry ◽  
Effective Prevention ◽  
Viral Infectious Disease ◽  
Sirna Knockdown

Porcine reproductive and respiratory syndrome (PRRS), a significant viral infectious disease that commonly occurs among farmed pigs, leads to considerable economic losses to the swine industry worldwide. Major vault protein (MVP) is a host factor that induces type Ⅰ interferon (IFN) production. In this study, we evaluated the effect of MVP on PRRSV infection in CRL2843CD163 cell lines and porcine alveolar macrophages (PAMs). Our results showed that MVP expression was downregulated by PRRSV infection. Adenoviral overexpression of MVP inhibited PRRSV replication, whereas the siRNA knockdown of MVP promoted PRRSV replication. In addition, MVP knockdown has an adverse effect on the inhibitive role of MVP overexpression on PRRSV replication. Moreover, MVP could induce the expression of type Ⅰ IFNs and IFN-stimulated gene 15 (ISG15) in PRRSV-infected PAMs. Based on these results, MVP may be a potential molecular target of drugs for the effective prevention and treatment of PRRSV infection.

Porcine 2′,5′-oligoadenylate synthetase-like protein inhibits replication of porcine reproductive and respiratory syndrome virus

2019 ◽  
Author(s):  
huawei li ◽  
ruining wang ◽  
wenjia wang ◽  
yinfeng kang ◽  
mengmeng zhao
Keyword(s):  
Alveolar Macrophages ◽  
Respiratory Syndrome Virus ◽  
Type I ◽  
Oligoadenylate Synthetase ◽  
Swine Industry ◽  
Exogenous Expression ◽  
Polymerase Chain ◽  
Interfering Rna ◽  
Inducible Gene

Abstract Background : Porcine reproductive and respiratory syndrome virus (PRRSV) is a serious pathogen that causes $664 million losses per year to the swine industry. There are few useful vaccines that can provide protection against PRRSV infection. 2′, 5′-oligoadenylate synthetase-like protein (OASL) has antiviral activity, this has not been shown for PRRSV and the mechanism is unknown. Methods : Expression of OASL in porcine alveolar macrophages induced by interferon (IFN)-b stimulation and PRRSV infection was examined by real-time polymerase chain reaction. Exogenous expression and knockdown of OASL were used to determine the role of OASL in the PRRSV replication cycle. The type I IFN signaling pathway was evaluated after OASL overexpression. Results : In this study, we found that the expression of OASL in porcine alveolar macrophages was significantly increased by IFN-b stimulation and PRRSV infection. Porcine-OASL-specific small interfering RNA (siRNA) promoted PRRSV replication, whereas exogenous expression of porcine OASL inhibited replication of the virus. The anti-PRRSV activity of porcine OASL was lost after knockdown of retinoic acid-inducible gene I ( DDX58 , also known as RIG-I ). Conclusions : Porcine OASL suppresses PRRSV replication.

scholarly journals Porcine Reproductive and Respiratory Syndrome Virus Induces IL-1βProduction Depending on TLR4/MyD88 Pathway and NLRP3 Inflammasome in Primary Porcine Alveolar Macrophages

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Jing Bi ◽  
Shuang Song ◽  
Liurong Fang ◽  
Dang Wang ◽  
Huiyuan Jing ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Alveolar Macrophages ◽  
Nlrp3 Inflammasome ◽  
Respiratory Syndrome Virus ◽  
Dependent Manner ◽  
Swine Industry ◽  
Downstream Signaling ◽  
Infection Treatment ◽  
Sirna Knockdown ◽  
Myd88 Pathway

Porcine reproductive and respiratory syndrome virus (PRRSV) is anArterivirusthat has been devastating the swine industry worldwide since the late 1980s. Previous studies have reported that PRRSV infection induced the production of IL-1β. However, the cellular sensors and signaling pathways involved in this process have not been elucidated yet. Here, we studied the mechanisms responsible for the production of IL-1βin response to highly pathogenic PRRSV. Upon PRRSV infection of primary porcine alveolar macrophages, both mRNA expression and secretion of IL-1βwere significantly increased in a time- and dose-dependent manner. We also investigated the role of several pattern-recognition receptors and adaptor molecules in this response and showed that the TLR4/MyD88 pathway and its downstream signaling molecules, NF-κB, ERK1/2, and p38 MAPKs, were involved in IL-1βproduction during PRRSV infection. Treatment with specific inhibitors or siRNA knockdown assays demonstrated that components of the NLRP3 inflammasome were crucial for IL-1βsecretion but not for IL-1βmRNA expression. Furthermore, TLR4/MyD88/NF-κB signaling pathway was involved in PRRSV-induced expression of NLRP3 inflammasome components. Together, our results deciphered the pathways leading from recognition of PRRSV to the production and release of IL-1β, providing a deeper knowledge of the mechanisms of PRRSV-induced inflammation responses.

scholarly journals Seroprevalences of classical swine fever virus and porcine reproductive and respiratory syndrome virus in pigs in Hunan Province, China

2020 ◽  
Author(s):  
Haoyang Yu ◽  
Luhua Zhang ◽  
Yunfeng Cai ◽  
Tao Peng ◽  
Lei Liu ◽  
...  
Keyword(s):  
Average Rate ◽  
Classical Swine Fever ◽  
Control Measures ◽  
Hunan Province ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Growth Stages ◽  
Serum Samples ◽  
Swine Industry ◽  
Effective Prevention

Abstract Background: Classical swine fever (CSF) and porcine reproductive and respiratory syndrome (PRRS) are responsible for major economic losses and represent a threat to the swine industry worldwide. Routine surveillance serology for CSF and PRRS will be critical to maintain the health status of sow farms in Hunan Province, which is one of the top pig production provinces in China.The objective of our study was to investigate the seroprevalence of CSF virus (CSFV) and PRRS virus (PRRSV) in Hunan Province from 2017 to 2019 using ELISA. The cohort pig serum samples were collected from vaccinated and unvaccinated sow farms in eight cities in Hunan Province. Results: CSFV and PRRSV seropositivity showed significant differences among parts of Hunan Province in China. Interestingly, our findings show that the level of CSFV antibody in piglet sera decreases gradually with increasing piglet age, whereas PRRSV-specific antibodies may appear in various growth stages in unvaccinated animals. Meanwhile, the average rate of CSFV antibody seropositivity was 82.2%, while the rate of PRRSV antibody seropositivity was slightly higher (84.4%) in the immunized group.Conclusions: The results from this study suggest that a serological investigation of these two major infectious diseases (CSF and PRRS) among pigs at various growth stages will provide a basis for the further development of more effective prevention and control measures.

scholarly journals Porcine Reproductive and Respiratory Syndrome Virus Evades Antiviral Innate Immunity via MicroRNAs Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuan Zhang ◽  
Wen-Hai Feng
Keyword(s):  
Innate Immunity ◽  
Immune Evasion ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Gene Expressions ◽  
Non Coding Rnas ◽  
New Treatments ◽  
Antiviral Innate Immunity

Porcine reproductive and respiratory syndrome (PRRS) is one of the most important diseases in pigs, leading to significant economic losses in the swine industry worldwide. MicroRNAs (miRNAs) are small single-stranded non-coding RNAs involved in regulating gene expressions at the post-transcriptional levels. A variety of host miRNAs are dysregulated and exploited by PRRSV to escape host antiviral surveillance and help virus infection. In addition, PRRSV might encode miRNAs. In this review, we will summarize current progress on how PRRSV utilizes miRNAs for immune evasions. Increasing knowledge of the role of miRNAs in immune evasion will improve our understanding of PRRSV pathogenesis and help us develop new treatments for PRRSV-associated diseases.

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.

MicroRNA-376b-3p Promotes Porcine Reproductive and Respiratory Syndrome Virus Replication by Targeting Viral Restriction Factor TRIM22

2021 ◽  
Author(s):  
Jing Chen ◽  
Shijie Zhao ◽  
Zhiying Cui ◽  
Wen Li ◽  
Pengli Xu ◽  
...  
Keyword(s):  
Viral Infections ◽  
Antiviral Effect ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Restriction Factor ◽  
Transcriptional Level ◽  
Swine Industry ◽  
Human Virus ◽  
N Protein ◽  
Novel Strategy

Porcine reproductive and respiratory syndrome virus is a major economically significant pathogen and has evolved several strategies to evade host's antiviral response and provide favorable conditions for survival. In the present study, we demonstrated that a host microRNA, miR-376b-3p, was upregulated by PRRSV infection through the viral components, nsp4 and nsp11, and miR-376b-3p can directly target tripartite motif-containing 22 (TRIM22) to impair its anti-PRRSV activity, thus facilitating the replication of PRRSV. Meanwhile, we found that TRIM22 induced degradation of the nucleocapsid protein (N) of PRRSV by interacting with N protein to inhibit PRRSV replication, and further study indicated that TRIM22 could enhance the activation of lysosomal pathway by interacting with LC3 to induce lysosomal degradation of N protein. In conclusion, PRRSV increased miR-376b-3p expression and hijacked the host miR-376b-3p to promote PRRSV replication by impairing the antiviral effect of TRIM22. Therefore, our finding outlines a novel strategy of immune evasion exerted by PRRSV, which is helpful for better understanding the pathogenesis of PRRSV. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) causes enormous economic losses each year in the swine industry worldwide. MicroRNAs (miRNAs) play important roles during viral infections via modulating the expression of viral or host genes at post-transcriptional level. TRIM22 has recently been identified as a key restriction factor that inhibited the replication of a number of human virus such as HIV, ECMV, HCV, HBV, IAV, and RSV. Here we showed that host miR-376b-3p could be up-regulated by PRRSV and functioned to impair the anti-PRRSV role of TRIM22 to facilitate PRRSV replication. Meanwhile, we found that TRIM22 inhibited the replication of PRRSV by interacting with viral N protein and accelerating its degradation through the lysosomal pathway. Collectively, the paper described a novel mechanism that PRRSV exploited the host miR-376b-3p to evade antiviral responses and provided a new insight into the study of virus-host interactions.

scholarly journals Porcine Reproductive and Respiratory Syndrome Virus Activates Lipophagy To Facilitate Viral Replication through Downregulation of NDRG1 Expression

2019 ◽  
Vol 93 (17) ◽  
Author(s):  
Jiang Wang ◽  
Jiao-Yang Liu ◽  
Ke-Yu Shao ◽  
Ying-Qian Han ◽  
Guo-Li Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Virus Assembly ◽  
Rna Virus ◽  
Progeny Virus ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Effective Strategies ◽  
Single Positive ◽  
Negative Role

ABSTRACTAutophagy maintains cellular homeostasis by degrading organelles, proteins, and lipids in lysosomes. Autophagy is involved in the innate and adaptive immune responses to a variety of pathogens. Some viruses can hijack host autophagy to enhance their replication. However, the role of autophagy in porcine reproductive and respiratory syndrome virus (PRRSV) infection is unclear. Here, we show that N-Myc downstream-regulated gene 1 (NDRG1) deficiency induced autophagy, which facilitated PRRSV replication by regulating lipid metabolism. NDRG1 mRNA is expressed ubiquitously in most porcine tissues and most strongly in white adipose tissue. PRRSV infection downregulated the expression of NDRG1 mRNA and protein, while NDRG1 deficiency contributed to PRRSV RNA replication and progeny virus assembly. NDRG1 deficiency reduced the number of intracellular lipid droplets (LDs), but the expression levels of key genes in lipogenesis and lipolysis were not altered. Our results also show that NDRG1 deficiency promoted autophagy and increased the subsequent yields of hydrolyzed free fatty acids (FFAs). The reduced LD numbers, increased FFA levels, and enhanced PRRSV replication were abrogated in the presence of an autophagy inhibitor. Overall, our findings suggest that NDRG1 plays a negative role in PRRSV replication by suppressing autophagy and LD degradation.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV), an enveloped single-positive-stranded RNA virus, causes acute respiratory distress in piglets and reproductive failure in sows. It has led to tremendous economic losses in the swine industry worldwide since it was first documented in the late 1980s. Vaccination is currently the major strategy used to control the disease. However, conventional vaccines and other strategies do not provide satisfactory or sustainable prevention. Therefore, safe and effective strategies to control PRRSV are urgently required. The significance of our research is that we demonstrate a previously unreported relationship between PRRSV, NDRG1, and lipophagy in the context of viral infection. Furthermore, our data point to a new role for NDRG1 in autophagy and lipid metabolism. Thus, NDRG1 and lipophagy will have significant implications for understanding PRRSV pathogenesis for developing new therapeutics.

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 Xanthohumol inhibits PRRSV proliferation and alleviates oxidative stress induced by PRRSV via the Nrf2–HMOX1 axis

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Xuewei Liu ◽  
Zhongbao Song ◽  
Juan Bai ◽  
Hans Nauwynck ◽  
Yongxiang Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Strategy ◽  
Antioxidant Response ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Related Factor ◽  
Nuclear Factor ◽  
Swine Industry ◽  
Therapeutic Drugs ◽  
Swine Pathogen

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen that causes significant economic losses in the global swine industry. Commercial vaccines provide limited protection against this virus, and no highly effective therapeutic drugs are yet available. In this study, we first screened a library of 386 natural products and found that xanthohumol (Xn), a prenylated flavonoid found in hops, displayed high anti-PRRSV activity by inhibiting PRRSV adsorption onto and internalization into cells. Transcriptome sequencing revealed that Xn treatment stimulates genes associated with the antioxidant response in the nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. Xn causes increased expression of Nrf2, HMOX1, GCLC, GCLM, and NQO1 in Marc-145 cells. The action of Xn against PRRSV proliferation depends on Nrf2 in Marc-145 cells and porcine alveolar macrophages (PAMs). This finding suggests that Xn significantly inhibits PRRSV proliferation and decreases viral-induced oxidative stress by activating the Nrf2–HMOX1 pathway. This information should be helpful for developing a novel prophylactic and therapeutic strategy against PRRSV infection.

scholarly journals Helicase of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Strain HV Reveals a Unique Structure

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 215 ◽  
Author(s):  
Chenjun Tang ◽  
Zengqin Deng ◽  
Xiaorong Li ◽  
Meiting Yang ◽  
Zizi Tian ◽  
...  
Keyword(s):  
Nonstructural Protein ◽  
Equine Arteritis Virus ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Multiple Processes ◽  
Multiple Domains ◽  
Functional Analyses ◽  
Zinc Binding Domain

Porcine reproductive and respiratory syndrome virus (PRRSV) is prevalent throughout the world and has caused great economic losses to the swine industry. Nonstructural protein 10 (nsp10) is a superfamily 1 helicase participating in multiple processes of virus replication and one of the three most conserved proteins in nidoviruses. Here we report three high resolution crystal structures of highly pathogenic PRRSV nsp10. PRRSV nsp10 has multiple domains, including an N-terminal zinc-binding domain (ZBD), a β-barrel domain, a helicase core with two RecA-like domains, and a C-terminal domain (CTD). The CTD adopts a novel fold and is required for the overall structure and enzymatic activities. Although each domain except the CTD aligns well with its homologs, PRRSV nsp10 adopts an unexpected extended overall structure in crystals and solution. Moreover, structural and functional analyses of PRRSV nsp10 versus its closest homolog, equine arteritis virus nsp10, suggest that DNA binding might induce a profound conformational change of PRRSV nsp10 to exert functions, thus shedding light on the mechanisms of activity regulation of this helicase.

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