scholarly journals Porcine Reproductive and Respiratory Syndrome Virus Reverse Genetics and the Major Applications

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1245
Author(s):  
Jayeshbhai Chaudhari ◽  
Hiep L. X. Vu
Keyword(s):  
Viral Genome ◽  
Reverse Genetics ◽  
Rna Virus ◽  
Site Directed Mutagenesis ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Cdna Clones ◽  
Swine Industry ◽  
Host Interaction ◽  
Foreign Genes

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive sense, single-stranded RNA virus that is known to infect only pigs. The virus emerged in the late 1980s and became endemic in most swine producing countries, causing substantial economic losses to the swine industry. The first reverse genetics system for PRRSV was reported in 1998. Since then, several infectious cDNA clones for PRRSV have been constructed. The availability of these infectious cDNA clones has facilitated the genetic modifications of the viral genome at precise locations. Common approaches to manipulate the viral genome include site-directed mutagenesis, deletion of viral genes or gene fragments, insertion of foreign genes, and swapping genes between PRRSV strains or between PRRSV and other members of the Arteriviridae family. In this review, we describe the approaches to construct an infectious cDNA for PRRSV and the ten major applications of these infectious clones to study virus biology and virus–host interaction, and to design a new generation of vaccines with improved levels of safety and efficacy.

scholarly journals Porcine Reproductive and Respiratory Syndrome Virus: Immune Escape and Application of Reverse Genetics in Attenuated Live Vaccine Development

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 480
Author(s):  
Honglei Wang ◽  
Yangyang Xu ◽  
Wenhai Feng
Keyword(s):  
Immune Responses ◽  
Reverse Genetics ◽  
Vaccine Development ◽  
Immune Escape ◽  
Rna Virus ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Live Vaccines ◽  
Host Immune Responses ◽  
Inactivated Vaccines

Porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus widely prevalent in pigs, results in significant economic losses worldwide. PRRSV can escape from the host immune response in several processes. Vaccines, including modified live vaccines and inactivated vaccines, are the best available countermeasures against PRRSV infection. However, challenges still exist as the vaccines are not able to induce broad protection. The reason lies in several facts, mainly the variability of PRRSV and the complexity of the interaction between PRRSV and host immune responses, and overcoming these obstacles will require more exploration. Many novel strategies have been proposed to construct more effective vaccines against this evolving and smart virus. In this review, we will describe the mechanisms of how PRRSV induces weak and delayed immune responses, the current vaccines of PRRSV, and the strategies to develop modified live vaccines using reverse genetics systems.

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.

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.

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 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 A Synthetic Porcine Reproductive and Respiratory Syndrome Virus Strain Confers Unprecedented Levels of Heterologous Protection

2015 ◽  
Vol 89 (23) ◽  
pp. 12070-12083 ◽  
Author(s):  
Hiep L. X. Vu ◽  
Fangrui Ma ◽  
William W. Laegreid ◽  
Asit K. Pattnaik ◽  
David Steffen ◽  
...  
Keyword(s):  
Reverse Genetics ◽  
Vaccine Coverage ◽  
Rna Virus ◽  
Respiratory Syndrome Virus ◽  
Full Genome ◽  
Genome Sequences ◽  
Prrsv Strain ◽  
Heterologous Protection

ABSTRACTCurrent vaccines do not provide sufficient levels of protection against divergent porcine reproductive and respiratory syndrome virus (PRRSV) strains circulating in the field, mainly due to the substantial variation of the viral genome. We describe here a novel approach to generate a PRRSV vaccine candidate that could confer unprecedented levels of heterologous protection against divergent PRRSV isolates. By using a set of 59 nonredundant, full-genome sequences of type 2 PRRSVs, a consensus genome (designated PRRSV-CON) was generated by aligning these 59 PRRSV full-genome sequences, followed by selecting the most common nucleotide found at each position of the alignment. Next, the synthetic PRRSV-CON strain was generated through the use of reverse genetics. PRRSV-CON replicates as efficiently as our prototype PRRSV strain FL12, bothin vitroandin vivo. Importantly, when inoculated into pigs, PRRSV-CON confers significantly broader levels of heterologous protection than does wild-type PRRSV. Collectively, our data demonstrate that PRRSV-CON can serve as an excellent candidate for the development of a broadly protective PRRSV vaccine.IMPORTANCEThe extraordinary genetic variation of RNA viruses poses a monumental challenge for the development of broadly protective vaccines against these viruses. To minimize the genetic dissimilarity between vaccine immunogens and contemporary circulating viruses, computational strategies have been developed for the generation of artificial immunogen sequences (so-called “centralized” sequences) that have equal genetic distances to the circulating viruses. Thus far, the generation of centralized vaccine immunogens has been carried out at the level of individual viral proteins. We expand this concept to PRRSV, a highly variable RNA virus, by creating a synthetic PRRSV strain based on a centralized PRRSV genome sequence. This study provides the first example of centralizing the whole genome of an RNA virus to improve vaccine coverage. This concept may be significant for the development of vaccines against genetically variable viruses that require active viral replication in order to achieve complete immune protection.

scholarly journals The 6K2 Protein and the VPg of Potato Virus A Are Determinants of Systemic Infection in Nicandra physaloides

1999 ◽  
Vol 12 (12) ◽  
pp. 1074-1081 ◽  
Author(s):  
Minna-Liisa Rajamäki ◽  
Jari P. T. Valkonen
Keyword(s):  
Amino Acid ◽  
Potato Virus ◽  
Viral Genome ◽  
Recombinant Virus ◽  
Systemic Infection ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Cdna Clones ◽  
Post Inoculation ◽  
Potato Virus A

Infection with the isolate PVA-M of potato virus A (PVA; genus Potyvirus) is restricted to the inoculated leaves of Nicandra physaloides (Solanaceae), whereas the isolate PVA-B11 infects plants systemically by 10 days post inoculation. Resistance to systemic infection was shown to develop during plant growth. A recombinant virus (B11-M) in which a 1,208-nucleotide sequence of the full-length cDNA clone of PVA-B11 was replaced with the corresponding sequence from PVA-M displayed a phenotype similar to that of PVA-M. The replaced sequence contained four amino acid differences between the two isolates: one in the 6K2 protein and three in the viral genome-linked protein (VPg). Site-directed mutagenesis of the cDNA clones and inoculation of the mutants to N. physaloides indicated that the amino acid substitutions of Met5Val in the 6K2 protein or Leu185Ser in the VPg permitted vascular movement and systemic infection. However, resistance was only partially overcome by these changes, since systemic infection proceeded at a slower rate than with PVA-B11. The amino acid substitution Val116Met in the VPg alone was sufficient to overcome resistance and recover the phenotype of the isolate PVA-B11. These data indicated that both the 6K2 protein and the VPg were avirulence determinants of PVA-M in N. physaloides and suggested a possibly coordinated function of them in the vascular movement of PVA.

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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