Spread Of Porcine Reproductive And Respiratory Syndrome Virus Research Articles

Untangling lineage introductions, persistence and transmission drivers of HP-PRRSV sublineage 8.7

Despite a rapid expansion of Porcine reproductive and respiratory syndrome virus (PRRSV) sublineage 8.7 over recent years, very little is known about the patterns of virus evolution, dispersal, and the factors influencing this dispersal. Relying on a national PRRSV surveillance project established over 20 years ago, we expand the available genomic data of sublineage 8.7 from China. We perform independent interlineage and intralineage recombination analyses for the entire study period, which showed a heterogeneous recombination pattern. A series of Bayesian phylogeographic analyses uncover the role of Guangdong as an important infection hub within Asia. The spatial spread of PRRSV is highly linked with a composite of human activities and the heterogeneous provincial distribution of the swine industry, largely propelled by the smaller-scale Chinese rural farming systems in the past years. We sequence all four available modified live vaccines (MLVs) and perform genomic analyses with publicly available data, of which our results suggest a key “leaky” period spanning 2011–2017 with two concurrent amino acid mutations in ORF1a 957 and ORF2 250. Overall, our study provides an in-depth overview of the evolution, transmission dynamics, and potential leaky status of HP-PRRS MLVs, providing critical insights into new MLV development.

Pathogenic Characteristics of Five Different Lineage of Korean PRRSV‐2 Isolates (NADC30‐Like, VR2332‐Like, LKA, LKB, and LKC)

Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant pathogen in the worldwide swine industry. The virus shows high genetic variation coupled with a broad range of virulence in pigs. Although multiple lineages of the virus have been prevalent throughout in Korea, the characteristics of lineage‐wise pathogenicity are largely unknown. Therefore, this study was designed to analyze and compare the pathogenicity of 11 representative Korean PRRSV‐2 isolates selected from PRRSV‐2 lineages circulating in Korea, NADC30‐like, VR2332‐like, and three nation‐specific lineages (lineage KOR A (LKA), lineage KOR B (LKB), and lineage KOR C (LKC)), which have been continuously prevalent in the nation. Eleven groups of pigs were experimentally infected with one Korean PRRSV‐2 isolate through four consecutive animal experiments. Body weight and body temperature were recorded during each 4‐week challenge experiment period, and virological, serological, and histopathological tests were performed on the collected samples. The data from the animal experiments were integrated into two indicators—excretion and clinical signs—through correlation and principal component analysis (PCA). Meta‐analysis was used to compare PRRSV‐2 isolates using each indicator. Based on these analyses, while L1C viruses used in this study (JB15‐N‐P31‐GB and JB15‐N‐PJ73‐GN, similar to NADC30‐like strains) exhibited low or moderate levels of excretion and clinical signs, lineage 5 (L5) or modified live vaccine (MLV)‐variant strains exhibited high levels of excretion compared to other PRRSV‐2 isolates. However, the L5 variants all caused mild clinical signs, except for JB15‐N‐PJ4‐GN, which showed the 4th highest clinical sign indicator. Among the Korean lineages (LKA, LKB, and LKC), two LKB strains (GGYC45 and JB15‐N‐PJ10‐GN) were the most virulent as they showed the highest mortality after the challenge. On the other hand, the LKA and LKC viruses displayed lower excretion indicators than L5 strains, but they had higher‐ranked clinical sign indicators than low‐virulence L5 MLV variants. In conclusion, PRRSV prevalent in Korea has diverse excretion and clinical characteristics, and certain lineage is highly pathogenic. These results will offer useful insights to prevent spread of PRRSV and improve the efficacy of vaccines in the future.

Spatiotemporal relative risk distribution of porcine reproductive and respiratory syndrome virus in the United States.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains widely distributed across the U.S. swine industry. Between-farm movements of animals and transportation vehicles, along with local transmission are the primary routes by which PRRSV is spread. Given the farm-to-farm proximity in high pig production areas, local transmission is an important pathway in the spread of PRRSV; however, there is limited understanding of the role local transmission plays in the dissemination of PRRSV, specifically, the distance at which there is increased risk for transmission from infected to susceptible farms. We used a spatial and spatiotemporal kernel density approach to estimate PRRSV relative risk and utilized a Bayesian spatiotemporal hierarchical model to assess the effects of environmental variables, between-farm movement data and on-farm biosecurity features on PRRSV outbreaks. The maximum spatial distance calculated through the kernel density approach was 15.3 km in 2018, 17.6 km in 2019, and 18 km in 2020. Spatiotemporal analysis revealed greater variability throughout the study period, with significant differences between the different farm types. We found that downstream farms (i.e., finisher and nursery farms) were located in areas of significant-high relative risk of PRRSV. Factors associated with PRRSV outbreaks were farms with higher number of access points to barns, higher numbers of outgoing movements of pigs, and higher number of days where temperatures were between 4°C and 10°C. Results obtained from this study may be used to guide the reinforcement of biosecurity and surveillance strategies to farms and areas within the distance threshold of PRRSV positive farms.

Genetic Variability and Recombination of the NSP2 Gene of PRRSV-2 Strains in China from 1996 to 2021.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most serious infectious diseases that detrimentally affects the pig industry worldwide. The disease, which is typically difficult to control, is an immunosuppressive disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV), the genome of which (notably the NSP2 gene) undergoes rapid mutation. In this study, we sought to determine the genetic variation in the PRRSV-2 NSP2 gene in China from 1996 to 2021. Strain information was obtained from the GenBank database and analyzed from a molecular epidemiological perspective. We compared the nucleotide and amino acid homologies of the NSP2 sequences of different PRRSV-2 lineages, and examined phylogenetic relationships based on an analysis of the NSP2 sequences of 122 strains. The results revealed that NADC-30-like strains, which are represented by lineage 1, and HP-PRRSV strains, which are represented by lineage 8, were the most prevalent in China from 1996 to 2021. Close similarities were detected in the genetic evolution of lineages 3, 5, and 8. For nucleotide and amino acid sequence comparisons, we selected representative strains from each lineage, and for the NSP2 among different PRRSV-2 strains, we accordingly detected homologies of 72.5-99.8% and 63.9-99.4% at the nucleotide and amino acid levels, respectively, thereby indicating certain differences in the degrees of NSP2 amino acid and nucleotide variation. Based on amino acid sequence comparisons, we identified deletions, insertions, and substitutions at multiple sites among the NSP2 sequences of PRRSV-2 strains. Recombination analysis revealed the occurrence of five recombinant events among the 135 selected PRRSV-2 strains, and that there is a high probability of recombination of lineage 1 strains. The findings of this study enabled us to gain an in-depth understanding of the prevalence of PRRSV in China over the past 25 years and will contribute to providing a theoretical basis for evolution and epidemiology of the spread of PRRSV.

TAT Nanobody Exerts Antiviral Effect against PRRSV In Vitro by Targeting Viral Nucleocapsid Protein.

Porcine reproductive and respiratory syndrome (PRRS) is caused by the PRRS virus (PRRSV), which has brought huge economic losses to the pork industry worldwide since its first discovery in the late 1980s in North America. To date, there are no effective commercial vaccines or therapeutic drugs available for controlling the spread of PRRSV. Due to their unique advantages of high affinity and high specificity, nanobodies (Nbs) have received increasing attention in the process of disease diagnosis and treatment. Trans-activator transcription (TAT) can serve as a vector to carry specific proteins into cells by passing through cell membranes. In our previous study, a specific Nb against the PRRSV nucleocapsid (N) protein was screened using phage display technology. For this study, we developed a novel recombinant protein constituting a TAT-conjugated Nb, which we call TAT-Nb1. The target cell entry efficiency of TAT-Nb1 and its effect on PRRSV infection and replication were then investigated. Our results indicate that TAT delivered Nb1 into Marc-145 cells and porcine alveolar macrophages (PAMs) in a dose- and time-dependent manner. Furthermore, TAT-Nb1 dose-dependently suppressed PRRSV infection and replication, where this antiviral effect was independent of PRRSV strain. Co-immunoprecipitation results revealed that Nb1 efficiently interacted with the N protein of PRRSV. Taken together, the presented results suggest that TAT-Nb1 can effectively suppress PRRSV replication, and it may be considered as a new anti-PRRSV candidate drug.

EGCG Restricts PRRSV Proliferation by Disturbing Lipid Metabolism.

ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV) infection leads to late-term reproductive failure and respiratory illness that affect the global swine industry. Epigallocatechin gallate (EGCG) is a polyphenolic compound from green tea that exerts antiviral activity against diverse viruses. This study aimed to report an uncharacterized mechanism of how EGCG restricted PRRSV proliferation. EGCG showed no significant effects on cell viability, cell cycle progression, and apoptosis in porcine alveolar macrophages and MARC-145 cells. The treatment of cells with EGCG attenuated the replication of both highly pathogenic and less pathogenic PRRSV in vitro. The viral life cycle analysis demonstrated that EGCG affected PRRSV replication and assembly, but not viral attachment, entry, or release. Interestingly, EGCG treatment abrogated the increased lipid droplets formation and lipid content induced by PRRSV infection. We further demonstrated that EGCG blocked PRRSV-stimulated expression of the key enzymes in lipid synthesis. In addition, EGCG attenuated PRRSV-induced autophagy that is critical for PRRSV proliferation. The supplementation of oleic acid restored PRRSV replication and assembly under EGCG treatment. Together, our results support that EGCG inhibits PRRSV proliferation through disturbing lipid metabolism.IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped single-positive-stranded RNA virus that causes acute respiratory distress in piglets and reproductive failure in sows, resulting in huge economic losses to the global swine industry. Several lines of evidence have suggested the crucial roles of lipids in PRRSV proliferation. Our previous report demonstrated that PRRSV activated lipophagy to facilitate viral replication through downregulating the expression of N-Myc downstream-regulated gene 1. The manipulation of lipid metabolism may be a new perspective to prevent PRRSV spread. In the present study, we reported that epigallocatechin-3-gallate (EGCG), the major component of green tea catechins, significantly attenuated PRRSV infection through inhibiting lipid synthesis and autophagy. Given that natural products derived from plants have helped in the prevention and treatment of various infectious diseases, EGCG has a great potential to serve as a safe and environmentally friendly natural compound to treat PRRSV infection.

Integrating animal movements with phylogeography to model the spread of PRRSV in the USA.

Viral sequence data coupled with phylodynamic models have become instrumental in investigating the outbreaks of human and animal diseases, and the incorporation of the hypothesized drivers of pathogen spread can enhance the interpretation from phylodynamic inference. Integrating animal movement data with phylodynamics allows us to quantify the extent to which the spatial diffusion of a pathogen is influenced by animal movements and contrast the relative importance of different types of movements in shaping pathogen distribution. We combine animal movement, spatial, and environmental data in a Bayesian phylodynamic framework to explain the spatial diffusion and evolutionary trends of a rapidly spreading sub-lineage (denoted L1A) of porcine reproductive and respiratory syndrome virus (PRRSV) Type 2 from 2014 to 2017. PRRSV is the most important endemic pathogen affecting pigs in the USA, and this particular virulent sub-lineage emerged in 2014 and continues to be the dominant lineage in the US swine industry to date. Data included 984 open reading frame 5 (ORF5) PRRSV L1A sequences obtained from two production systems in a swine-dense production region (∼85,000 mi2) in the USA between 2014 and 2017. The study area was divided into sectors for which model covariates were summarized, and animal movement data between each sector were summarized by age class (wean: 3–4 weeks; feeder: 8–25 weeks; breeding: ≥21 weeks). We implemented a discrete-space phylogeographic generalized linear model using Bayesian evolutionary analysis by sampling trees (BEAST) to infer factors associated with variability in between-sector diffusion rates of PRRSV L1A. We found that between-sector spread was enhanced by the movement of feeder pigs, spatial adjacency of sectors, and farm density in the destination sector. The PRRSV L1A strain was introduced in the study area in early 2013, and genetic diversity and effective population size peaked in 2015 before fluctuating seasonally (peaking during the summer months). Our study underscores the importance of animal movements and shows, for the first time, that the movement of feeder pigs (8–25 weeks old) shaped the spatial patterns of PRRSV spread much more strongly than the movements of other age classes of pigs. The inclusion of movement data into phylodynamic models as done in this analysis may enhance our ability to identify crucial pathways of disease spread that can be targeted to mitigate the spatial spread of infectious human and animal pathogens.

Modelling the transmission and vaccination strategy for porcine reproductive and respiratory syndrome virus.

Many aspects of the porcine reproductive and respiratory syndrome virus (PRRSV) between-farm transmission dynamics have been investigated, but uncertainty remains about the significance of farm type and different transmission routes on PRRSV spread. We developed a stochastic epidemiological model calibrated on weekly PRRSV outbreaks accounting for the population dynamics in different pig production phases, breeding herds, gilt development units, nurseries and finisher farms, of three hog producer companies. Our model accounted for indirect contacts by the close distance between farms (local transmission), between-farm animal movements (pig flow) and reinfection of sow farms (re-break). The fitted model was used to examine the effectiveness of vaccination strategies and complementary interventions such as enhanced PRRSV detection and vaccination delays and forecast the spatial distribution of PRRSV outbreak. The results of our analysis indicated that for sow farms, 59% of the simulated infections were related to local transmission (e.g. airborne, feed deliveries, shared equipment) whereas 36% and 5% were related to animal movements and re-break, respectively. For nursery farms, 80% of infections were related to animal movements and 20% to local transmission; while at finisher farms, it was split between local transmission and animal movements. Assuming that the current vaccines are 1% effective in mitigating between-farm PRRSV transmission, weaned pigs vaccination would reduce the incidence of PRRSV outbreaks by 3%, indeed under any scenario vaccination alone was insufficient for completely controlling PRRSV spread. Our results also showed that intensifying PRRSV detection and/or vaccination pigs at placement increased the effectiveness of all simulated vaccination strategies. Our model reproduced the incidence and PRRSV spatial distribution; therefore, this model could also be used to map current and future farms at-risk. Finally, this model could be a useful tool for veterinarians, allowing them to identify the effect of transmission routes and different vaccination interventions to control PRRSV spread.

Traveling Wave Solutions of a Four Dimensional Reaction-Diffusion Model for Porcine Reproductive and Respiratory Syndrome with Time Dependent Infection Rate

Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failure in sows and respiratory disease in piglets and growing pigs. The disease rapidly spreads in swine populations, making it a serious problem causing great financial losses to the swine industry. However, past mathematical models used to describe the spread of the disease have not yielded sufficient understanding of its spatial transmission. This work has been designed to investigate a mathematical model for the spread of PRRSV considering both time and spatial dimensions as well as the observed decline in infectiousness as time progresses. Moreover, our model incorporates into the dynamics the assumption that some members of the infected population may recover from the disease and become immune. Analytical solutions are derived by using the modified extended hyperbolic tangent method with the introduction of traveling wave coordinate. We also carry out a stability and phase analysis in order to obtain a clearer understanding of how PRRSV spreads spatially through time.

Association between management factors and herd status regarding Porcine Reproductive and Respiratory Syndrome virus infection - An analysis in the course of a voluntary PRRSV control program in Saxony and Thuringia

In Saxony and Thuringia, federal states of Germany with a low density of commercial pig farms, a voluntary program aims at controlling porcine reproductive and respiratory syndrome virus (PRRSV) infection. This targets the eradication of the infection on a herd level which has previously been achieved in a subset of herds. The presented study aimed at identifying management factors related with a positive or a negative PRRSV antibody (AB status) or PRRSV genome status (PCR status) on a herd level. Data were collected in 82 farms in a region implementing a voluntary PRRSV control program. The test findings for the years 2011 to 2018 were compiled for each year and associated with the interrogated parameters. A generalized linear mixed model was used to identify factors associated with the AB and PCR status. The variables "separation of contaminated and non-contaminated areas on the loading ramp" (p = 0.012), "separation of gilts and sows" (p = 0.017) and "recording of visitors in a book" (p = 0.046) were negatively associated with the PCR status. In contrast, "separation of gilts and finishers" (p = 0.044) as well as the existence of "separated alleyways" (p = 0.042) were positively related to the PCR status. "Vaccination against PRRSV" was positively associated with the AB status and the PCR status (p = 0.005 and p = 0.001, respectively). In numerous variables, a low variability was observed. Certain biosecurity measures to control the movement of animals (separation of contaminated and not contaminated areas on the loading ramp) or people (recording of visitors) contribute to a successful reduction of PRRSV infections and a negative herd status. A combination of different measures may reduce PRRSV spread within pig herds. Breaking the infection cycle in gilts, either by separation of gilts from older sows or immunization, may be considered as a key aspect, presumably additionally supported by keeping gilts together with fattening pigs.

Epidemiology investigation of PRRSV discharged by faecal and genetic variation of ORF5.

To obtain more information of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) transmission via faeces in/between farms, 360 swine faecal samples were randomly collected from different farms in China from 2017 to 2019. Sixty-two ORF5 genes were amplified by PCR from 120 positive samples identified by real-time RT-PCR and further characterized by sequencing. Phylogenetic analysis based on the ORF5 gene revealed that these strains can be divided into four lineages: lineage 1 (NADC30-like), lineage 3 (QYYZ-like), lineage 5.1 (VR2332-like) and lineage 8.7 (JXA1-like), with 62.9% (39/62) NADC30-like virus, 21% (13/62) QYYZ-like virus, 1.6% (1/62) VR2332-like virus and 14.5% (9/62) for JAX1-like virus. In particular, 14 PRRSVs including lineage 1, 5.1 and 8.7 can be isolated from 120 positive faecal samples, which further suggests that faecal transmission may be an important factor in the spread of PRRSV in farms. Full-length genome sequencing analysis showed that 14 isolates share 83.1%-97.7% homology with each other and 82.3%-96.1% identity with NADC30, 83.2%-99.7% with VR2332, 79.6%-87.2% with QYYZ and 82.6%-98.9% with JXA1 and CH-1a, and only 60.1%-60.7% with LV. Recombination events were observed in the six out of 14 strains. Collectively, the data of this study are useful for understanding the spread of PRRSV via faeces. Additionally, the virus was isolated from positive faecal samples, suggesting that faecal transmission may be an important factor in the spread of PRRSV in farms.

Investigations on spreading of PRRSV among swine herds by improved minimum spanning network analysis

In Hungary, the economic losses caused by porcine reproductive and respiratory syndrome virus (PRRSV) led to the launching of a national PRRSV Eradication Program. An important element of the program was investigating the spread of PRRSV among swine herds and the possible ways of introduction by sequencing of the open reading frame 5 (ORF5) gene. However, the classical phylogenetic tree presentation cannot explain several genetic relationships clearly, while more precise visualization can be represented by network tree diagram. In this paper, we describe a practical and easy-to-follow enriched minimum spanning similarity network application for improved representation of phylogenetic relations among viral strains. This method eliminated the necessity of applying a predefined, arbitrary cut-off or computationally extensive algorithms. The network-based visualization allowed processing and visualizing large amount of data equally for the laboratory, private and official veterinarians, and helped identify the potential connections between different viral sequences that support data-driven decisions in the eradication program. By applying network analysis, previously unknown epidemiological connections between infected herds were identified, and virus spreading was analyzed within short period of time. In our study, we successfully built and applied network analysis tools in the course of the Hungarian PRRSV Eradication Program.

Porcine reproductive and respiratory syndrome virus dissemination across pig production systems in the United States

Porcine reproductive and respiratory syndrome virus (PRRSV) remains widespread in the North American pig population. Despite improvements in virus characterization, it is unclear whether PRRSV infections are a product of viral circulation within production systems (local) or across production systems (external). Here, we examined the local and external dissemination dynamics of PRRSV and the processes facilitating its spread in three production systems. Overall, PRRSV genetic diversity has declined since 2018, while phylodynamic results support frequent external transmission. We found that PRRSV dissemination predominantly occurred mostly through transmission between farms of different production companies for several months, especially from November until May, a timeframe already established as PRRSV season. Although local PRRSV dissemination occurred mainly through regular pig flow (from sow to nursery and then to finisher farms), an important flux of PRRSV dissemination also occurred in the opposite direction, from finisher to sow and nursery farms, highlighting the importance of downstream farms as sources of the virus. Our results also showed that farms with pig densities of 500 to 1,000 pig/km2 and farms located at a range within 0.5km and 0.7km from major roads were more likely to be infected by PRRSV, whereas farms at an elevation of 41 to 61 meters and surrounded by denser vegetation were less likely to be infected, indicating their role as dissemination barriers. In conclusion, our results demonstrate that external dissemination was intense, and reinforce the importance of farm proximity on PRRSV spread. Thus, consideration of farm location, geographic characteristics and animal densities across production systems may help to forecast PRRSV collateral dissemination.

Pathogenicity of porcine reproductive and respiratory syndrome virus (ORF5 RFLP 1-7-4 viruses) in China.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus that causes reproductive failure in sows and respiratory problems in piglets. PRRSV infection leads to substantial pig mortality and causing huge economic losses so that disease outbreaks caused by the new PRRSV strain from other regions have caused great concern in China. In this study, we analysed the pathogenicity of the novel ORF5 RFLP 1-7-4-like PRRSV strain, named PRRSV-ZDXYL-China-2018-1 in pigs. The viral challenge test showed that PRRSV-ZDXYL-China-2018-1 infection can cause persistent fever, moderate dyspnoea, serum viraemia and interstitial pneumonia in piglets. The levels of viral loads in serum and PRRSV-specific antigen were also detected in lung tissues were used one-step Taq-Man RT-qPCR and Immunohistochemistry, respectively. At 28dpi, the level of specific antibodies was increased among infected piglets. Importantly, the new virus appeared be a moderately virulent isolate with pathogenicity compared to HP-PRRSV strain LQ (JXA1-like strain). Histological examination revealed severe monocyte haemorrhage and interstitial pneumonia associated with monocyte infiltration in the lung tissue of pigs infected with PRRSV-ZDXYL-China-2018-1 and LQ-JXA1 strains. Immunohistochemistry (IHC) results showed positive brown-red epithelial cells and macrophages in pig lungs. Therefore, it is critical to establish an effective strategy to control the spread of PRRSV in China.

Contrasting animal movement and spatial connectivity networks in shaping transmission pathways of a genetically diverse virus

Analyses of livestock movement networks has become key to understanding an industry’s vulnerability to infectious disease spread and for identifying farms that play disproportionate roles in pathogen dissemination. In addition to animal movements, many pathogens can spread between farms via mechanisms mediated by spatial proximity. Heterogeneities in contact patterns based on spatial proximity are less commonly considered in network studies, and studies that jointly consider spatial connectivity and animal movement are rare. The objective of this study was to determine the extent to which movement versus spatial proximity networks determine the distribution of an economically important endemic virus, porcine reproductive and respiratory syndrome virus (PRRSV), within a swine-dense region of the U.S. PRRSV can be classified into numerous phylogenetic lineages. Such data can be used to better resolve between-farm infection chains and elucidate types of contact most associated with transmission. Here, we construct movement and spatial proximity networks; farms within the networks were classified as cases if a given PRRSV lineage had been recovered at least once in a year for each of three years analyzed. We evaluated six lineages and sub-lineages across three years, and evaluated the epidemiological relevance of each network by applying network k-tests to statistically evaluate whether the pattern of case occurrence within the network was consistent with transmission via network linkages. Our results indicated that animal movements, not local area spread, play a dominant role in shaping transmission pathways, though there were differences amongst lineages. The median number of case farms inter-linked via animal movements was approximately 4.1x higher than random expectations (range: 1.7–13.7; p < 0.05, network k-test), whereas this measure was only 2.7x higher than random expectations for farms linked via spatial proximity (range: 1.3–5.4; p < 0.05, network k-test). For spatial proximity networks, contact based on proximities of <5 km appeared to have greater epidemiological relevance than longer distances, likely related to diminishing probabilities of local area spread at greater distances. However, the greater overall levels of connectivity of the spatial network compared to the movement network highlights the vulnerability of pig populations to widespread transmission via this route. By combining genetic data with network analysis, this research advances our understanding of dynamics of between-farm spread of PRRSV, helps establish the relative importance of transmission via animal movements versus local area spread, and highlights the potential for targeted control strategies based upon heterogeneities in network connectivity.

A model for porcine reproductive and respiratory syndrome with time-dependent infection rate: traveling wave solution

Porcine reproductive and respiratory syndrome (PRRS) gives rise to reproductive disorders in sows and problem with respiratory system in piglets and young pigs. This disease creates serious economic losses to major pork producing countries. The disease, which is characterized by high morbidity and significant mortality, combined with its potential for rapid spread, can devastate the pig industries of the affected countries. However, not much is known about the spatial transmission of PRRSV (porcine reproductive and respiratory syndrome virus) in growing pigs. In previous models, the infection rate has been assumed to be constant with time. Experimental studies on specific cases of this viral infection suggest that this assumption might not hold. A structured model for the spread of PRRSV has therefore been constructed, incorporating time and spatial dimensions as well as the decline of infection rate with time. Using the traveling wave coordinate and the modified extended hyperbolic tangent method, we derive analytical solutions to the model system. Stability and phase plane analyses are also carried out in order to gain insights into the spatial spread of PRRS as time progresses.

A conjugate protein containing HIV TAT, ISG20, and a PRRSV polymerase binding inhibits PRRSV replication and may be a novel therapeutic platform

Porcine Reproductive and Respiratory Syndrome (PRRS), which is caused by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection, has caused substantial economic losses for the global swine industry. To date, there are limited commercially available measures to control the spread of PRRSV. The available vaccines are unstable and there is no anti-PRRSV therapeutic available. Therefore, this study designed a novel recombinant antiviral protein that included a novel polypeptide that binds to the PRRSV polymerase (p9), the transduction ability of the HIV TAT, and the nucleotide degradation activity of interferon stimulated gene 20 (ISG20). The recombinant proteins TAT-p9-ISG20 and p9-ISG20 were expressed in MARC-145 cells by transient transfection and then tested for antiviral activity and entry efficiency. The p9-ISG20 construct had greater antiviral activity than either p9 alone (1.37-fold) or ISG20 alone (1.9-fold). Addition of the HIV TAT protein increased the entry efficiency of p9-ISG20 by 1.57-fold, which was associated with increased anti-viral activity (1.52-fold) compared to P9-ISG20. In summary, TAT-p9-ISG20 achieved a synergistic effect by combining three different antiviral proteins and may be a novel PRRSV therapeutic platform.

Epidemiological investigations of the introduction of porcine reproductive and respiratory syndrome virus in Chile, 2013-2015.

Porcine reproductive and respiratory syndrome (PRRS) is endemic in most pork producing countries. In Chile, eradication of PRRS virus (PRRSV) was successfully achieved in 2009 as a result of the combined efforts of producers and the animal health authorities. In October 2013, after several years without detecting PRRSV under surveillance activities, suspected cases were confirmed on a commercial swine farm. Here, we describe the PRRS epidemic in Chile between October 2013 and April 2015, and we studied the origins and spread of PRRSV throughout the country using official surveillance data and Bayesian phylogenetic analysis. Our results indicate that the outbreaks were caused by a PRRSV closely related to viruses present in swine farms in North America, and different from the strain that circulated in the country before 2009. Using divergence time estimation analysis, we found that the 2013–2015 PRRSV may have been circulating in Chile for at least one month before the first detection. A single strain of PRRSV spread into a limited number of commercial and backyard swine farms. New infections in commercial systems have not been reported since October 2014, and eradication is underway by clearing the disease from the few commercial and backyard farms that remain positive. This is one of the few documented experiences of PRRSV introduction into a disease-free country.

Estimation of Time-Dependent Reproduction Numbers for Porcine Reproductive and Respiratory Syndrome across Different Regions and Production Systems of the US.

Porcine reproductive and respiratory syndrome (PRRS) is, arguably, the most impactful disease for the North American swine industry, due to its known considerable economic losses. The Swine Health Monitoring Project (SHMP) monitors and reports weekly new PRRS cases in 766 sow herds across the US. The time-dependent reproduction number (TD-R) is a measure of a pathogen’s transmissibility. It may serve to capture and report PRRS virus (PRRSV) spread at the regional and system levels. The primary objective of the study here was to estimate the TD-R values for PRRSV using regional and system-level PRRS data, and to contrast it with commonly used metrics of disease, such as incidence estimates and space–time clusters. The second objective was to test whether the estimated TD-Rs were homogenous across four US regions. Retrospective monthly incidence data (2009–2016) were available from the SHMP. The dataset was divided into four regions based on location of participants, and demographic and environmental features, namely, South East (North Carolina), Upper Midwest East (UME, Minnesota/Iowa), Upper Midwest West (Nebraska/South Dakota), and South (Oklahoma panhandle). Generation time distributions were fit to incidence data for each region, and used to calculate the TD-Rs. The Kruskal–Wallis test was used to determine whether the median TD-Rs differed across the four areas. Furthermore, we used a space–time permutation model to assess spatial–temporal patterns for the four regions. Results showed TD-Rs were right skewed with median values close to “1” across all regions, confirming that PRRS has an overall endemic nature. Variation in the TD-R patterns was noted across regions and production systems. Statistically significant periods of PRRSV spread (TD-R > 1) were identified for all regions except UME. A minimum of three space–time clusters were detected for all regions considering the time period examined herein; and their overlap with “spreader events” identified by the TD-R method varied according to region. TD-Rs may help to measure PRRS spread to understand, in quantitative terms, disease spread, and, ultimately, support the design, implementation, and monitoring of interventions aimed at mitigating the impact of PRRSV spread in the US.

Applications of Bayesian Phylodynamic Methods in a Recent U.S. Porcine Reproductive and Respiratory Syndrome Virus Outbreak.

Classical phylogenetic methods such as neighbor-joining or maximum likelihood trees, provide limited inferences about the evolution of important pathogens and ignore important evolutionary parameters and uncertainties, which in turn limits decision making related to surveillance, control, and prevention resources. Bayesian phylodynamic models have recently been used to test research hypotheses related to evolution of infectious agents. However, few studies have attempted to model the evolutionary dynamics of porcine reproductive and respiratory syndrome virus (PRRSV) and, to the authors' knowledge, no attempt has been made to use large volumes of routinely collected data, sometimes referred to as big data, in the context of animal disease surveillance. The objective of this study was to explore and discuss the applications of Bayesian phylodynamic methods for modeling the evolution and spread of a notable 1-7-4 RFLP-type PRRSV between 2014 and 2015. A convenience sample of 288 ORF5 sequences was collected from 5 swine production systems in the United States between September 2003 and March 2015. Using coalescence and discrete trait phylodynamic models, we were able to infer population growth and demographic history of the virus, identified the most likely ancestral system (root state posterior probability = 0.95) and revealed significant dispersal routes (Bayes factor > 6) of viral exchange among systems. Results indicate that currently circulating viruses are evolving rapidly, and show a higher level of relative genetic diversity over time, when compared to earlier relatives. Biological soundness of model results is supported by the finding that sow farms were responsible for PRRSV spread within the systems. Such results cannot be obtained by traditional phylogenetic methods, and therefore, our results provide a methodological framework for molecular epidemiological modeling of new PRRSV outbreaks and demonstrate the prospects of phylodynamic models to inform decision-making processes for routine surveillance and, ultimately, to support prevention and control of food animal disease at local and regional scales.