scholarly journals Bottlenecks in the transmission of Porcine reproductive and respiratory syndrome virus (PRRSV1) to naïve pigs and quasi-species variation during infection in partially immune pigs

2018 ◽  
Author(s):  
Martí Cortey ◽  
Gastón Arocena ◽  
Emanuela Pileri ◽  
Gerard Martín-Valls ◽  
Enric Mateu
Keyword(s):  
Immune Response ◽  
Disease Transmission ◽  
Vaccine Development ◽  
Rna Virus ◽  
Respiratory Syndrome Virus ◽  
Species Variation ◽  
Prrs Virus ◽  
M Proteins ◽  
Positive Sense ◽  
Important Disease

AbstractThe existence of bottlenecks during infection of Porcine reproductive and respiratory syndrome virus (PRRSV) was studied in an experimental one-to-one model of transmission in pigs. Besides, the differences between viral quasi-species in vaccinated pigs that developed shorter or longer viremias after natural challenge were analysed. The results consistently reported the existence of bottlenecks during transmission. Several positions along the PRRSV genome were identified as being selected in partially immune animals that developed short viremias. Those positions accumulated in GP2, nsp9 and M proteins and resulted in changes in the protein structure and in the interactions of those proteins with their targets. The fact that the affected proteins are known targets of the immunity against PRRSV suggested that the immune response selected those changes. This pig model can be useful for the study of other pathogens of interest in animals and humans.Author summaryPorcine reproductive and respiratory syndrome (PRRS) is one of the most economically important disease of pigs. It is caused by PRRS virus (PRRSV), a positive-sense, single-stranded RNA virus in the Arteriviridae family within the order Nidovirales. Here, we study the existence of bottlenecks during disease transmission and the differences between viral quasi-species in vaccinated pigs that developed shorter or longer viremias after natural challenge. Our results consistently report the existence of bottlenecks during PRRSV1 transmission and identify several mutations along the viral genome selected by the host immune response that can be clear targets for new vaccine development.

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 Challenges for Porcine Reproductive and Respiratory Syndrome (PRRS) Vaccine Design: Reviewing Virus Glycoprotein Interactions with CD163 and Targets of Virus Neutralization

2019 ◽  
Vol 6 (1) ◽  
pp. 9 ◽  
Author(s):  
Ana Stoian ◽  
Raymond Rowland
Keyword(s):  
Vaccine Development ◽  
Noncovalent Interactions ◽  
Rna Virus ◽  
Neutralizing Antibody ◽  
Complex Surface ◽  
Surface Proteins ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Live Virus ◽  
Potential Vaccine

One of the main participants associated with the onset and maintenance of the porcine respiratory disease complex (PRDC) syndrome is porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus that has plagued the swine industry for 30 years. The development of effective PRRS vaccines, which deviate from live virus designs, would be an important step towards the control of PRRS. Potential vaccine antigens are found in the five surface proteins of the virus, which form covalent and multiple noncovalent interactions and possess hypervariable epitopes. Consequences of this complex surface structure include antigenic variability and escape from immunity, thus presenting challenges in the development of new vaccines capable of generating broadly sterilizing immunity. One potential vaccine target is the induction of antibody that disrupts the interaction between the macrophage CD163 receptor and the GP2, GP3, and GP4 heterotrimer that protrudes from the surface of the virion. Studies to understand this interaction by mapping mutations that appear following the escape of virus from neutralizing antibody identify the ectodomain regions of GP5 and M as important immune sites. As a target for antibody, GP5 possesses a conserved epitope flanked by N-glycosylation sites and hypervariable regions, a pattern of conserved epitopes shared by other viruses. Resolving this apparent conundrum is needed to advance PRRS vaccine development.

scholarly journals CD8+T Cell-Mediated Immunity duringTrypanosoma cruziInfection: A Path for Vaccine Development?

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Fernando dos Santos Virgilio ◽  
Camila Pontes ◽  
Mariana Ribeiro Dominguez ◽  
Jonatan Ersching ◽  
Mauricio Martins Rodrigues ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Disease Transmission ◽  
Vaccine Development ◽  
Experimental Studies ◽  
Chronic Phase ◽  
Protozoan Parasite ◽  
Active Role ◽  
Cell Mediated Immunity ◽  
High Proliferative Activity

MHC-restrictedCD8+T cells are important during infection with the intracellular protozoan parasiteTrypanosoma cruzi, the causative agent of Chagas disease. Experimental studies performed in the past 25 years have elucidated a number of features related to the immune response mediated by these T cells, which are important for establishing the parasite/host equilibrium leading to chronic infection.CD8+T cells are specific for highly immunodominant antigens expressed by members of thetrans-sialidase family. After infection, their activation is delayed, and the cells display a high proliferative activity associated with high apoptotic rates. Although they participate in parasite control and elimination, they are unable to clear the infection due to their low fitness, allowing the parasite to establish the chronic phase when these cells then play an active role in the induction of heart immunopathology. Vaccination with a number of subunit recombinant vaccines aimed at eliciting specificCD8+T cells can reverse this path, thereby generating a productive immune response that will lead to the control of infection, reduction of symptoms, and reduction of disease transmission. Due to these attributes, activation ofCD8+T lymphocytes may constitute a path for the development of a veterinarian or human vaccine.

scholarly journals Aptamer-Based QCM-Sensor for Rapid Detection of PRRS Virus

Proceedings ◽  
2018 ◽  
Vol 2 (13) ◽  
pp. 1038
Author(s):  
Chakpetch Kuitio ◽  
Kiattawee Choowongkomon ◽  
Peter A. Lieberzeit
Keyword(s):  
Classical Swine Fever Virus ◽  
Rapid Detection ◽  
Quartz Crystal ◽  
Pseudorabies Virus ◽  
Rna Virus ◽  
Classical Swine Fever ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Virus Particles ◽  
Prrs Virus

Porcine reproductive and respiratory syndrome (PRRS) is caused by an RNA virus and has substantial economic impact on swine industry. Screening pigs for infection is the best way to prevent spreading the disease. For that purpose, we developed biosensors based on aptamers, i.e., short ss-DNA that can bind to porcine reproductive and respiratory syndrome virus (PRRSV). The present study, demonstrates selectivity and sensitivity of PRRSV aptamer (7R) by the means of quartz crystal microbalance (QCM) measurements. The respective results show that 7R aptamer indeed binds to samples containing around 1010 PRRSV virus particles, but not to Pseudorabies virus (PRV) and Classical swine fever virus (CSFV).

scholarly journals Exploring COVID-19: Relating the spike protein to infectivity, pathogenicity and Immunogenicity

2021 ◽  
Vol 5 (1) ◽  
pp. 001-010
Author(s):  
Nikhra Vinod
Keyword(s):  
Immune Response ◽  
Life Cycle ◽  
Host Cell ◽  
Disease Transmission ◽  
Vaccine Development ◽  
Spike Protein ◽  
Structural Proteins ◽  
Causative Organism ◽  
S Protein ◽  
New Variant

Introduction: SARS-CoV-2 life cycle: The disease which reportedly began in Chinese city Wuhan in November-December 2019 manifesting as severe respiratory illness, soon spread to various parts of the world, and was named COVID-19, and declared a pandemic by WHO. The life cycle of SARS-CoV-2 begins with membrane fusion mediated by Spike (S) protein binding to the ACE2 receptors. Following viral entry and release of genome into the host cell cytoplasm there occurs replication and transcription to generate viral structural and non-structural proteins. Finally, VLPs are produced and the mature virions are released from the host cell. Immunogenicity of the spike protein: The S protein is considered the main antigenic component among structural proteins of SARS-CoV-2 and responsible for inducing the host immune response. The neutralising antibodies (nAbs) targeting the S protein are produced and may confer a protective immunity against the viral infection. Further, the role of the S protein in infectivity also makes it an important tool for diagnostic antigen-based testing and vaccine development. The S-specific antibodies, memory B and circulating TFH cells are consistently elicited following SARS-CoV-2 infection, and COVID-19 vaccine shots in clinical trials. The emerging SARS-CoV-2 variants: The early genomic variations in SARS-CoV-2 have gone almost unnoticed having lacked an impact on disease transmission or its clinical course. Some of the recently discovered mutations, however, have impact on transmissibility, infectivity, or immune response. One such mutation is the D614G variant, which has increased in prevalence to currently become the dominant variant world-over. Another, relatively new variant, named VUI-202012/01 or B.1.1.7 has acquired 17 genomic alterations and carries the risk of enhanced infectivity. Further, its potential impact on vaccine efficacy is a worrisome issue. Conclusion: THE UNMET CHALLENGES: COVID-19 as a disease and SARS-CoV-2 as its causative organism, continue to remain an enigma. While we continue to explore the agent factors, disease transmission dynamics, pathogenesis and clinical spectrum of the disease, and therapeutic modalities, the grievous nature of the disease has led to emergency authorizations for COVID-19 vaccines in various countries. Further, the virus may continue to persist and afflict for years to come, as future course of the disease is linked to certain unknown factors like effects of seasonality on virus transmission and unpredictable nature of immune response to the disease.

scholarly journals COVID-19 Vaccine Candidates: Prediction and Validation of 174 SARS-CoV-2 Epitopes

2020 ◽  
Author(s):  
Marek Prachar ◽  
Sune Justesen ◽  
Daniel Bisgaard Steen-Jensen ◽  
Stephan Thorgrimsen ◽  
Erik Jurgons ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Development ◽  
Rna Virus ◽  
Binding Prediction ◽  
Prediction Tools ◽  
High Prediction ◽  
Circulating T Cells ◽  
Hla Binding ◽  
Efficacious Vaccine

AbstractThe recent outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a large RNA virus and testing of all overlapping peptides in vitro to deconvolute an immune response is not feasible. Therefore HLA-binding prediction tools are often used to narrow down the number of peptides to test. We tested 19 epitope-HLA-binding prediction tools, and using an in vitro peptide MHC stability assay, we assessed 777 peptides that were predicted to be good binders across 11 MHC allotypes. In this investigation of potential SARS-CoV-2 epitopes we found that current prediction tools vary in performance when assessing binding stability, and they are highly dependent on the MHC allotype in question. Designing a COVID-19 vaccine where only a few epitope targets are included is therefore a very challenging task. Here, we present 174 SARS-CoV-2 epitopes with high prediction binding scores, validated to bind stably to 11 HLA allotypes. Our findings may contribute to the design of an efficacious vaccine against COVID-19.

scholarly journals Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marek Prachar ◽  
Sune Justesen ◽  
Daniel Bisgaard Steen-Jensen ◽  
Stephan Thorgrimsen ◽  
Erik Jurgons ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Development ◽  
Rna Virus ◽  
Epitope Prediction ◽  
Binding Prediction ◽  
Prediction Tools ◽  
Low Performance ◽  
Hla Binding ◽  
Efficacious Vaccine

AbstractThe outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a large RNA virus and testing of all of its overlapping peptides in vitro to deconvolute an immune response is not feasible. Therefore HLA-binding prediction tools are often used to narrow down the number of peptides to test. We tested NetMHC suite tools' predictions by using an in vitro peptide-MHC stability assay. We assessed 777 peptides that were predicted to be good binders across 11 MHC alleles in a complex-stability assay and tested a selection of 19 epitope-HLA-binding prediction tools against the assay. In this investigation of potential SARS-CoV-2 epitopes we found that current prediction tools vary in performance when assessing binding stability, and they are highly dependent on the MHC allele in question. Designing a COVID-19 vaccine where only a few epitope targets are included is therefore a very challenging task. Here, we present 174 SARS-CoV-2 epitopes with high prediction binding scores, validated to bind stably to 11 HLA alleles. Our findings may contribute to the design of an efficacious vaccine against COVID-19.

scholarly journals Crystal Structure of Porcine Reproductive and Respiratory Syndrome Virus Leader Protease Nsp1α

2009 ◽  
Vol 83 (21) ◽  
pp. 10931-10940 ◽  
Author(s):  
Yuna Sun ◽  
Fei Xue ◽  
Yu Guo ◽  
Ming Ma ◽  
Ning Hao ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Biological Function ◽  
Rna Virus ◽  
Foot And Mouth Disease ◽  
Zinc Ion ◽  
Molecular Surface ◽  
Structural Basis ◽  
Respiratory Syndrome Virus ◽  
Prrs Virus ◽  
Positive Strand Rna

ABSTRACT Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV), a positive-strand RNA virus that belongs to the Arteriviridae family of Nidovirales, has been identified as the causative agent of PRRS. Nsp1α is the amino (N)-terminal protein in a polyprotein encoded by the PRRSV genome and is reported to be crucial for subgenomic mRNA synthesis, presumably by serving as a transcription factor. Before functioning in transcription, nsp1α proteolytically releases itself from nsp1β. However, the structural basis for the self-releasing and biological functions of nsp1α remains elusive. Here we report the crystal structure of nsp1α of PRRSV (strain XH-GD) in its naturally self-processed form. Nsp1α contains a ZF domain (which may be required for its biological function), a papain-like cysteine protease (PCP) domain with a zinc ion unexpectedly bound at the active site (which is essential for proteolytic self-release of nsp1α), and a carboxyl-terminal extension (which occupies the substrate binding site of the PCP domain). Furthermore, we determined the exact location of the nsp1α self-processing site at Cys-Ala-Met180↓Ala-Asp-Val by use of crystallographic data and N-terminal amino acid sequencing. The crystal structure also suggested an in cis self-processing mechanism for nsp1α. Furthermore, nsp1α appears to have a dimeric architecture both in solution and as a crystal, with a hydrophilic groove on the molecular surface that may be related to nsp1α's biological function. Compared with existing structure and function data, our results suggest that PRRSV nsp1α functions differently from other reported viral leader proteases, such as that of foot-and-mouth disease.

scholarly journals miR-541-3p Promoted Porcine Reproductive and Respiratory Syndrome Virus 2 (PRRSV-2) Replication by Targeting Interferon Regulatory Factor 7

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 126
Author(s):  
Xibao Shi ◽  
Yuanhao Yang ◽  
Xiaozhuan Zhang ◽  
Xiaobo Chang ◽  
Jing Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Type I Interferon ◽  
Interferon Regulatory Factor ◽  
Respiratory Syndrome Virus ◽  
Type I ◽  
Regulatory Factor ◽  
Prrs Virus ◽  
Interferon Regulatory Factor 7 ◽  
Host Innate Immune Response ◽  
And Control

Porcine reproductive and respiratory syndrome (PRRS) is a disease caused by PRRS virus (PRRSV), which seriously harms the pig industry. Revealing the mechanism by which PRRSV inhibits immune response will help prevent and control PRRS. Here, we found that PRRSV-2 may hijack host miR-541-3p to inhibit host innate immune response. Firstly, this work showed that miR-541-3p mimics could facilitate the replication of PRRSV-2 and the results of the quantitative real time polymerase chain reaction (qRT-PCR) showed that PRRSV-2 could up-regulate the expression of miR-541-3p in MARC-145 cells. Since previous studies have shown that type I interferon could effectively inhibit the replication of PRRSV-2, the present work explored whether miR-541-3p regulated the expression of type I interferon and found that miR-541-3p could negatively regulate the transcription of type I interferon by targeting interferon regulatory factor 7 (IRF7). More importantly, PRRSV-2 infection could down-regulate the expression of IRF7 and over-expression of IRF7 could down-regulate the replication of PRRSV-2 in MARC-145 cells. In conclusion, PRRSV-2 infection up-regulated the expression of miR-541-3p to promote its replication in MARC-145 cells, since miR-541-3p can negatively regulate the transcription of type I interferon by targeting IRF7.

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