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 Integrated time-serial transcriptome networks reveal common innate and tissue-specific adaptive immune responses to PRRSV infection

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Byeonghwi Lim ◽  
Sangwook Kim ◽  
Kyu-Sang Lim ◽  
Chang-Gi Jeong ◽  
Seung-Chai Kim ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Vaccine Development ◽  
Expression Patterns ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Specific Group ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Gene Expression Control

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) infection is the most important viral disease causing severe economic losses in the swine industry. However, mechanisms underlying gene expression control in immunity-responsible tissues at different time points during PRRSV infection are poorly understood. We constructed an integrated gene co-expression network and identified tissue- and time-dependent biological mechanisms of PRRSV infection through bioinformatics analysis using three tissues (lungs, bronchial lymph nodes [BLNs], and tonsils) via RNA-Seq. Three groups with specific expression patterns (i.e., the 3-dpi, lung, and BLN groups) were discovered. The 3 dpi-specific group showed antiviral and innate-immune signalling similar to the case for influenza A infection. Moreover, we observed adaptive immune responses in the lung-specific group based on various cytokines, while the BLN-specific group showed down-regulated AMPK signalling related to viral replication. Our study may provide comprehensive insights into PRRSV infection, as well as useful information for vaccine development.

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 Genetically barcoded SIV reveals the emergence of escape mutations in multiple viral lineages during immune escape

2019 ◽  
Vol 117 (1) ◽  
pp. 494-502
Author(s):  
Taina T. Immonen ◽  
Celine Camus ◽  
Carolyn Reid ◽  
Christine M. Fennessey ◽  
Gregory Q. Del Prete ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Escape ◽  
Rhesus Macaques ◽  
Quantitative Measure ◽  
Population Level ◽  
Therapeutic Interventions ◽  
Viral Escape ◽  
Virus Population ◽  
Host Immune Responses ◽  
Immune Pressure

The rapidity of replication coupled with a high mutation rate enables HIV to evade selective pressures imposed by host immune responses. Investigating the ability of HIV to escape different selection forces has generally relied on population-level measures, such as the time to detectable escape mutations in plasma and the rate these mutations subsequently take over the virus population. Here we employed a barcoded synthetic swarm of simian immunodeficiency virus (SIV) in rhesus macaques to investigate the generation and selection of escape mutations within individual viral lineages at the Mamu-A*01-restricted Tat-SL8 epitope. We observed the persistence of more than 1,000 different barcode lineages following selection after acquiring escape mutations. Furthermore, the increased resolution into the virus population afforded by barcode analysis revealed changes in the population structure of the viral quasispecies as it adapted to immune pressure. The high frequency of emergence of escape mutations in parallel viral lineages at the Tat-SL8 epitope highlights the challenge posed by viral escape for the development of T cell-based vaccines. Importantly, the level of viral replication required for generating escape mutations in individual lineages can be directly estimated using the barcoded virus, thereby identifying the level of efficacy required for a successful vaccine to limit escape. Overall, assessing the survival of barcoded viral lineages during selection provides a direct and quantitative measure of the stringency of the underlying genetic bottleneck, making it possible to predict the ability of the virus to escape selective forces induced by host immune responses as well as during therapeutic interventions.

scholarly journals Molecular Mechanisms of Immune Escape for Foot-and-Mouth Disease Virus

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 729
Author(s):  
Bo Yang ◽  
Xiaohui Zhang ◽  
Dajun Zhang ◽  
Jing Hou ◽  
GuoWei Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Virus ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Host Immune Responses ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Vesicular Disease

Foot-and-mouth disease virus (FMDV) causes a highly contagious vesicular disease in cloven-hoofed livestock that results in severe consequences for international trade, posing a great economic threat to agriculture. The FMDV infection antagonizes the host immune responses via different signaling pathways to achieve immune escape. Strategies to escape the cell immune system are key to effective infection and pathogenesis. This review is focused on summarizing the recent advances to understand how the proteins encoded by FMDV antagonize the host innate and adaptive immune responses.

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 Neutralization of rhesus cytomegalovirus IL-10 reduces horizontal transmission and alters long-term immunity

2019 ◽  
Vol 116 (26) ◽  
pp. 13036-13041 ◽  
Author(s):  
Jesse D. Deere ◽  
W. L. William Chang ◽  
Andradi Villalobos ◽  
Kimberli A. Schmidt ◽  
Ashlesha Deshpande ◽  
...  
Keyword(s):  
Immune Responses ◽  
Persistent Infection ◽  
Vaccine Development ◽  
Rhesus Macaques ◽  
Horizontal Transmission ◽  
Severe Disease ◽  
Interleukin 10 ◽  
Primate Model ◽  
Host Immune Responses ◽  
Rhesus Cytomegalovirus

Human cytomegalovirus (HCMV) causes severe disease in infants and immunocompromised people. There is no approved HCMV vaccine, and vaccine development strategies are complicated by evidence of both persistent infection and reinfection of people with prior immunity. The greatest emphasis has been placed on reducing transmission to seronegative pregnant women to prevent vertical transmission and its potentially severe sequelae. Increasing evidence suggests that the earliest host–HCMV interactions establish conditions for viral persistence, including evasion of host immune responses to the virus. Using a nonhuman primate model of HCMV infection, we show that rhesus macaques immunized against viral interleukin-10 (IL-10) manifest delayed rhesus cytomegalovirus (RhCMV) acquisition and altered immune responses to the infection when it does occur. Among animals with the greatest antiviral IL-10–neutralizing activity, the timing of RhCMV seroconversion was delayed by an average of 12 weeks. After acquisition, such animals displayed an antibody response to the new infection, which peaked as expected after 2 weeks but then declined rapidly. In contrast, surprisingly, vaccination with glycoprotein B (gB) protein had no discernible impact on these outcomes. Our results demonstrate that viral IL-10 is a key regulator of successful host immune responses to RhCMV. Viral IL-10 is, therefore, an important target for vaccine strategies against cytomegalovirus (CMV). Furthermore, given the immunoregulatory function of viral IL-10, targeting this protein may prove synergistic with other vaccine therapies and targets. Our study also provides additional evidence that the earliest host–CMV interactions can have a significant impact on the nature of persistent infection.

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 Detection of Newcastle Disease Virus Minor Genetic Variants by Modified Single-Stranded Conformational Polymorphism Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Lukasz Rabalski ◽  
Krzysztof Smietanka ◽  
Zenon Minta ◽  
Boguslaw Szewczyk
Keyword(s):  
Newcastle Disease ◽  
Diagnostic Method ◽  
Rna Virus ◽  
Economic Losses ◽  
Polymorphism Analysis ◽  
Gene Encoding ◽  
Conformational Polymorphism ◽  
Live Vaccines ◽  
Single Stranded Conformational Polymorphism ◽  
Pathogenic Virus

Newcastle disease and Avian Influenza are considered to be the most dangerous fowl diseases which may cause huge economic losses. Newcastle disease is caused by the enveloped, and single-stranded RNA virus (NDV, APMV-1; belonging to Paramyxoviridae family), which can be further divided into sixteen different genotypes grouped into five pathotypes according to their pathogenicity. It has been reported that low pathogenic virus can greatly increase its pathogenicity even during a single passage. Additionally, due to the widespread use of live vaccines, a mixture of two or more different viruses in one sample can be detected. Hence, there is a great need for establishment of fast, inexpensive, sensitive, and relatively simple diagnostic method for multistrain and quasispecies detection of NDV infection. In this paper we describe a diagnostic method based on RT-PCR followed by a modified version of single-stranded conformational polymorphism analysis using short DNA fragments of gene encoding viral F protein. The method allows for rapid diagnosis of genetic variant emerging from previously stable population which may prevent the spread of the pathogenic viral variant.

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