Gastric ulcers in finishing pigs: the evaluation of selected non-dietary risk factors and impact on production performance.

BACKGROUND: The complex aetiology of gastric lesions in pigs remains largely unknown and effective preventive measures and pharmaceutical treatment of the disease have not been developed yet. Regardless of the fact that the overwhelming majority of previous research works dealing with gastric ulceration in pigs focused on the role of the nutritional determinants, including chemical composition of feeds, cereal type, finely ground pelleted diets, and feed additives, conclusions presented therein remain highly ambiguous. Thus, the purpose of this study was to evaluate the impact of the disease on production performance, and investigate the influence of selected non-dietary risk factors on the prevalence of gastric alterations in finishing pigs reared under conditions of 11 modern farms located in Poland. RESULTS: A total number of 26,043 finishing pigs was examined. 15,228 (58.47%) had gastric ulcers. Intact stomachs were detected in 6176 animals (23.71%). Parakeratosis and erosion were observed in 2551 (9.80%) and 2088 (8.02%), respectively. Among eight continuous variables two were found to be significantly associated with prevalence of the gastric ulcer: the growing number of animals in the herd, which was negatively correlated (P = 0.002; ρ = -0.37), and the growing average entry weight of animals transported to the finisher farm (P = 0.047; ρ = 0.24), which increased the risk of gastric ulcers prevalence. Among 12 nominal variables, problems with the quality of farm management (P = 0.041), and usage of straw as a bedding material (P = 0.002) were identified as determinants significantly associated with occurrence of the analysed health problem. CONCLUSIONS: Among 20 non-nutritional variables analysed in our study only few factors were found to be associated with the prevalence of the disease. The impact of broadly understood management issues on gastric health in finishing pigs deserves further research.

Genetic Diversity of Type A Influenza Viruses Found in Swine Herds in Northwestern Poland from 2017 to 2019: The One Health Perspective.

Influenza A viruses (IAV) are still a cause of concern for public health and veterinary services worldwide. With (-) RNA-segmented genome architecture, influenza viruses are prone to reassortment and can generate a great variety of strains, some capable of crossing interspecies barriers. Seasonal IAV strains continuously spread from humans to pigs, leading to multiple reassortation events with strains endemic to swine. Due to its high adaptability to humans, a reassortant strain based on "human-like" genes could potentially be a carrier of avian origin segments responsible for high virulence, and hence become the next pandemic strain with unseen pathogenicity. The rapid evolution of sequencing methods has provided a fast and cost-efficient way to assess the genetic diversity of IAV. In this study, we investigated the genetic diversity of swine influenza viruses (swIAVs) collected from Polish farms. A total of 376 samples were collected from 11 farms. The infection was confirmed in 112 cases. The isolates were subjected to next-generation sequencing (NGS), resulting in 93 full genome sequences. Phylogenetic analysis classified 59 isolates as genotype T (H1avN2g) and 34 isolates as genotype P (H1pdmN1pdm), all of which had an internal gene cassette (IGC) derived from the H1N1pdm09-like strain. These data are consistent with evolutionary trends in European swIAVs. The applied methodology proved to be useful in monitoring the genetic diversity of IAV at the human-animal interface.

Complex interplay between PRRSV-1 genetic diversity, coinfections and antimicrobial use influences performance parameters in post-weaning pigs.

Porcine reproductive and respiratory syndrome (PRRS) is one of the main diseases of pigs, leading to large economic losses in swine production worldwide. PRRSV high mutation rate and low cross-protection between strains make PRRS control challenging. Through a semi-longitudinal approach, we analysed the relationships among performance parameters, PRRSV-1 genetic diversity, coinfections and antimicrobial use (AMU) in pig nurseries. We collected data over the course of five years in five PRRS-positive nurseries belonging to an Italian multisite operation, for a total of 86 batches and over 200,000 weaners involved. The farm experienced a severe PRRS outbreak in the farrowing unit at the onset of the study, but despite adopting vaccination of all sows, batch-level losses in nurseries in the following years remained constantly high (mean±SE: 11.3 ± 0.5 %). Consistently with previous studies, our phylogenetic analysis of ORF 7 sequences highlighted the peculiarity of strains circulating in Italy. Greater genetic distances between the strain circulating in a weaners' batch and strains from the farrowing unit and the previous batch were associated with increased mortality (p < 0.0001). All the respiratory and enteric coinfections contributed to an increase in losses (all p < 0.026), with secondary infections by Streptococcus suis and enteric bacteria also inducing an increase in AMU (both p < 0.041). Our findings highlight that relying solely on sows' vaccination is insufficient to contain PRRS losses, and the implementation of rigorous biosecurity measures is pivotal to limit PRRSV circulation among pig flows and consequently minimise the risk of exposure to genetically diverse strains that would increase production costs.

Successful Whole Genome Nanopore Sequencing of Swine Influenza A Virus (swIAV) Directly from Oral Fluids Collected in Polish Pig Herds.

Influenza A virus (IAV) is a single-stranded, negative-sense RNA virus and a common cause of seasonal flu in humans. Its genome comprises eight RNA segments that facilitate reassortment, resulting in a great variety of IAV strains. To study these processes, the genetic code of each segment should be unraveled. Fortunately, new third-generation sequencing approaches allow for cost-efficient sequencing of IAV segments. Sequencing success depends on various factors, including proper sample storage and processing. Hence, this work focused on the effect of storage of oral fluids and swIAV sequencing. Oral fluids (n = 13) from 2017 were stored at -22 °C and later transferred to -80 °C. Other samples (n = 21) were immediately stored at -80 °C. A reverse transcription quantitative PCR (RT-qPCR) pre- and post-storage was conducted to assess IAV viral loads. Next, samples were subjected to two IAV long-read nanopore sequencing methods to evaluate success in this complex matrix. A significant storage-associated loss of swIAV loads was observed. Still, a total of 17 complete and 6 near-complete Polish swIAV genomes were obtained. Genotype T, (H1avN2, seven herds), P (H1N1pdm09, two herds), U (H1avN1, three herds), and A (H1avN1, 1 herd) were circulated on Polish farms. In conclusion, oral fluids can be used for long-read swIAV sequencing when considering appropriate storage and segment amplification protocols, which allows us to monitor swIAV in an animal-friendly and cost-efficient manner.

European and American Strains of Porcine Parainfluenza Virus 1 (PPIV-1) Belong to Two Distinct Genetic Lineages.

Porcine parainfluenza virus 1 (PPIV-1) is a recently emerged respirovirus closely related to human parainfluenza virus 1 (HPIV-1) and Sendai virus (SenV). PPIV-1 has been detected in Asia, the Americas and Europe, but knowledge on its epidemiology and genetic diversity is very limited. In the present study, the complete nucleotide sequences of the fusion (F)-protein gene obtained from samples from 12 Polish and 11 US herds were analysed and compared to previously available genetic data from the Americas, Asia and Europe. The existence of two distinct clades was observed, grouping European sequences and one Hong Kong sequence (clade 1), or one American sequence and three Asian sequences (clade 2). The mean genetic distances measured with the p-distance were 0.04 (S.E., 0.000) within both clades, and 0.095 (S.E., 0.006) between the clades. Moreover, two distinct clusters of highly similar sequences were identified, which corresponded to the geographically distant nurseries and finishing units, from three pig flows within one Polish pig-production company. The obtained data indicate that the two PPIV-1 lineages may have evolved independently in Europe and America. More studies, particularly involving Asian viruses, are necessary to understand the virus' emergence and epidemiology and the role of carriers in the spread of PPIV-1.

Detection of Porcine Respirovirus 1 (PRV1) in Poland: Incidence of Co-Infections with Influenza A Virus (IAV) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in Herds with a Respiratory Disease.

Porcine respirovirus 1 (PRV1) is also known as porcine parainfluenza virus 1 (PPIV1). The prevalence and the role of PRV1 infections for pig health is largely unknown. In order to assess the PRV1 prevalence in Poland, nasal swabs and oral fluids collected from pigs from 30 farms were examined with RT real-time PCR. Additionally, IAV and PRRSV infection statuses of PRV1-positive samples were examined. The results showed that the virus is highly prevalent (76.7% farms positive) and different patterns of PRV1 circulation in herds with mild-moderate respiratory disease were observed. Co-infections with IAV and PRRSV were infrequent and detected in 8 (23.5%) and 4 (11.8%) out of 34 PRV1-positive nasal swab pools from diseased pens, respectively. In one pen PRV1, IAV, and PRRSV were detected at the same time. Interestingly, PRV1 mean Ct value in samples with co-infections was significantly lower (29.8 ± 3.1) than in samples with a single PRV1 infection (32.5 ± 3.6) (p < 0.05), which suggested higher virus replication in these populations. On the other hand, the virus detection in pig populations exhibiting respiratory clinical signs, negative for PRRSV and IAV, suggests that PRV1 should be involved in differential diagnosis of respiratory problems.

ICTV Virus Taxonomy Profile: Arteriviridae 2021.

The family Arteriviridae comprises enveloped RNA viruses with a linear, positive-sense genome of approximately 12.7 to 15.7 kb. The spherical, pleomorphic virions have a median diameter of 50-74 nm and include eight to eleven viral proteins. Arteriviruses infect non-human mammals in a vector-independent manner. Infections are often persistent and can either be asymptomatic or produce overt disease. Some arteriviruses are important veterinary pathogens while others infect particular species of wild rodents or African non-human primates. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Arteriviridae, which is available at ictv.global/report/arteriviridae.

Wide Range of the Prevalence and Viral Loads of Porcine Circovirus Type 3 (PCV3) in Different Clinical Materials from 21 Polish Pig Farms.

Porcine circovirus type 3 (PCV3) was described in different clinical cases and healthy pigs. However, little is known about its circulation in pig farms. In order to assess PCV3 prevalence in 21 Polish farms, serum, feces, and oral fluid samples were examined by quantitative real-time PCR. In total, 1451 pairs of serum and feces from the same animals, as well as 327 samples of oral fluids were analyzed. The results showed that PCV3 is more commonly detected in oral fluids (37.3% positives) than in serum (9.7% positives) or feces (15.0% positives) samples. The viral loads detected in these materials ranged from 102.5-107.2 genome equivalent copies/mL. Although in most farms PCV3 was detected post weaning, in nine farms, the virus was also found in groups of suckling piglets, and in six of them viremia was detected. In four farms with reproductive failure, fetal materials were also obtained. PCV3 was detected in 36.0% of fetuses or stillborn piglets (9/25) with viral loads of 103.1-1010.4 genome equivalent copies/mL. In summary, the virus circulation may show different patterns, and congenital or early infection is not uncommon. Precise quantification of PCV3 loads in clinical materials seems to be necessary for the study and diagnosis of the infection.

Metagenomic sequencing of clinical samples reveals a single widespread clone of Lawsonia intracellularis responsible for porcine proliferative enteropathy.

Lawsonia intracellularis is a Gram-negative obligate intracellular bacterium that is the aetiological agent of proliferative enteropathy (PE), a common intestinal disease of major economic importance in pigs and other animal species. To date, progress in understanding the biology of L. intracellularis for improved disease control has been hampered by the inability to culture the organism in vitro. In particular, our understanding of the genomic diversity and population structure of clinical L. intercellularis is very limited. Here, we utilized a metagenomic shotgun approach to directly sequence and assemble 21 L. intracellularis genomes from faecal and ileum samples of infected pigs and horses across three continents. Phylogenetic analysis revealed a genetically monomorphic clonal lineage responsible for infections in pigs, with distinct subtypes associated with infections in horses. The genome was highly conserved, with 94 % of genes shared by all isolates and a very small accessory genome made up of only 84 genes across all sequenced strains. In part, the accessory genome was represented by regions with a high density of SNPs, indicative of recombination events importing novel gene alleles. In summary, our analysis provides the first view of the population structure for L. intracellularis, revealing a single major lineage associated with disease of pigs. The limited diversity and broad geographical distribution suggest the recent emergence and clonal expansion of an important livestock pathogen.

A recombination between two Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-1) vaccine strains has caused severe outbreaks in Danish pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) is prevalent in Danish swine herds. In July 2019, PRRSV-1 was detected in a PRRSV-negative boar station and subsequently spread to more than 38 herds that had received semen from the boar station. Full genome sequencing revealed a sequence of 15.098 nucleotides. Phylogenetic analyses showed that the strain was a recombination between the Amervac strain (Unistrain PRRS vaccine; Hipra) and the 96V198 strain (Suvaxyn PRRS; Zoetis AH). The major parent was the 96V198 strain that spanned ORFs 1-2 and part of ORF 3 and the minor parent was the Amervac strain, which constituted the remaining part of the genome. The virus seems to be highly transmissible and has caused severe disease in infected herds despite a high level of genetic identity to the attenuated parent strains. The source of infection was presumable a neighbouring farm situated 5.8 km from the boar station.

Do porcine parvoviruses 1 through 7 (PPV1-PPV7) have an impact on porcine circovirus type 2 (PCV2) viremia in pigs?

Infections with porcine parvoviruses 1 through 7 (PPV1-PPV7) and porcine circovirus type 2 (PCV2) are widespread in pig population. PCV2 is involved in a number of disease syndromes collectively called PCV2-associated diseases (PCVD). It is well elucidated, that PPV1 may act as a triggering factor of PCVD through supporting PCV2 replication. Less is known about the PPV2-PPV7 impact on PCV2 viremia, but several authors suggested an association between these viruses. In order to provide a better understanding of PCV2 and PPVs co-infections, 519 serum samples from eight Polish swine farms were tested by real-time PCR to assess the possible impact of PPV1-PPV7 on PCV2 viremia. Among all 519 serum samples, 30.6 % were positive for PCV2 and PPVs detection rates ranged from 2.9 % (PPV1) to 26.6 % (PPV2). Within 159 serum samples categorized as PCV2-positive, the prevalence rates of PPVs ranged from 7.5 % (PPV1) to 37.1 % (PPV6). The level of PCV2 viremia was significantly higher only in serum samples positive for PPV1 and PPV7 compared to samples negative for these PPVs. Moreover, the correlation between Ct values for PPV7 and PCV2 was observed. Thus, our results suggested that apart from PPV1, also PPV7 stimulate the replication of PCV2.

Real-Time PCR Detection Patterns of Porcine Circovirus Type 2 (PCV2) in Polish Farms with Different Statuses of Vaccination against PCV2.

Porcine circovirus type 2 (PCV2) is a globally spread pathogen controlled with generally highly efficacious vaccination protocols. In order to compare PCV2 detection profiles in farms with different vaccination statuses, serum (359) and fecal pools (351) and oral fluids (209) from four farms that do not vaccinate against PCV2 (NON-VAC) and from 22 farms that do vaccinate (VAC) were tested with quantitative real-time PCR. Additionally, nucleotide sequences of ORF2 of the virus were obtained from selected samples. Three genotypes, PCV2a, PCV2b, and PCV2d, were detected. Significant differences (p < 0.05) in PCV2 prevalence and quantities between the VAC and NON-VAC farms were evident. In five VAC farms, no viremia or shedding in feces was detected. On the other hand, in four VAC farms, the results were very similar to those from NON-VAC farms. No significant difference in PCV2 prevalence in oral fluids was observed between VAC and NON-VAC farms. An examination of viremia can be recommended for the detection of vaccination efficacy issues. The median of the PCV2 viral loads >6.0 log10 copies/mL in pooled sera from the vaccinated population should be considered a very strong indication that the vaccination protocol needs revision.

Does porcine circovirus type 3 (PCV3) interfere with porcine circovirus type 2 (PCV2) vaccine efficacy?

PCV2 is globally spread pathogen involved in a number of diseases (PCVD). Commonly used vaccines against PCV2 are proved to be highly efficacious. The role of recently discovered PCV3 for pig health and interference with PCV2 remains unknown. The study performed on serum samples from seven farms vaccinated against PCV2 and four non-vaccinated showed very low prevalence of PCV2 viremia in the former (3 out of 106 positive serum pools) and high prevalence of PCV2 viremia in the latter (35 out of 60 positive pools). Mean log10 PCV2 genome equivalents were lower in vaccinated farms (4.8 ± 0.6 log10  copies/ml) than in non-vaccinated farms (6.3 ± 1.3 log10  copies/ml). PCV3 was detected in 31 out of 106 and 12 out of 60 serum pools from vaccinated and non-vaccinated farms, respectively. Mean log10 PCV3 genome equivalents were significantly (p < 0.05) lower in vaccinated farms (3.9 ± 0.8 log10  copies/ml) than in non-vaccinated farms (4.4 ± 0.6 log10  copies/ml). Concurrent PCV2 and PCV3 infection was rare and found only in 1 out of 529 and 4 out of 292 individual serum samples from vaccinated and non-vaccinated farms, respectively. Our results showed lack of impact of PCV3 circulation on PCV2 vaccine efficacy. On the other hand, intensive PCV2 circulation and high viremia detected in non-vaccinated farms did not seem to increase the level of PCV3 infection.

Detection Patterns of Porcine Parvovirus (PPV) and Novel Porcine Parvoviruses 2 through 6 (PPV2-PPV6) in Polish Swine Farms.

Porcine parvovirus (PPV) is a major causative agent in reproductive failure, but in the last two decades many novel porcine parvoviruses were described and designated as porcine parvovirus 2 through 6 (PPV2-PPV6). However, their role for pig health is largely unknown. The aim of this study was to better understand the on-farm prevalence of PPVs in different age groups of pigs, and to assess the diagnostic applicability of testing different diagnostic materials. In total, 271 oral fluids, 1244 serum samples, and 1238 fecal samples were collected from 3-21-week-old pigs from 19 farms, and after pooling by 4-6, tested by real-time PCR. The results showed that PPVs are widely spread in Poland and that the highest detection rates were obtained for oral fluids (ranging from 10.7% (PPV1) to 48.7% (PPV2)). Fattening pigs were the age group with the most frequent detection of PPVs (ranging from 8.6% (PPV1) to 49.1% (PPV2)). Porcine parvoviruses were detected mostly in growing-finishing pigs and the infection persisted until the late fattening period, which may suggest the chronic character of the infection (especially for PPV2, which was found to commonly infect animals of all ages). Particularly low Ct values detected for PPV2, PPV3, PPV5, and PPV6 in serum pools from some farms suggested that these viruses may cause high levels of viremia in one or more individuals included in these pools. Further studies are needed to quantify the levels of PPVs viremia and to assess the impact in co-infections with other, often endemic pig viruses, such as porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV).

In vitro characterization of PRRSV isolates with different in vivo virulence using monocyte-derived macrophages.

The recent emergence of highly pathogenic porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) strains has caused severe economic losses. The biological elements defining virulence and pathogenicity are still unclear. In vitro characteristics using natural target cells of PRRSV provide important information to understand the basis of virulence at the cellular level, and provide a mean to reduce animal experimentations to achieve this goal. Here, we compared PRRSV strains from two geographically different regions, with varying in vivo characteristics, in terms of their interactions with monocyte-derived macrophages (MDMs). The strains included Lena and BOR59 from Belarus, and ILI6 from Russia, as well as PR11 and PR40, both from Italy. As a reference, we used a cell culture-adapted version of Lelystad, LVP. MDMs were pre-treated with IFNγ, IL-4 or IFNß, in order to understand responses in polarized and antiviral MDMs. In general, independent of the geographical origin, the strains with high virulence infected a higher percentage of MDMs and replicated to higher titers. These virulence-dependent differences were most pronounced when the MDMs had been treated with IFNß. Differentiation between intermediate and low virulent PRRSV was difficult, due to variations between different experiments, but LVP differed clearly from all field strains. IFNα and IL-10 were not detected in any experiment, but PR40 induced TNF and IL-1ß. Taken together, these results validate the MDM model to understand pathogenicity factors of PRRSV and confirm the importance of the escape from type I and II IFN-mediated effects for PRRSV virulence.

Comparison of six commercial ELISAs for the detection of antibodies against porcine reproductive and respiratory syndrome virus (PRRSV) in field serum samples.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most common infectious diseases of swine globally. Since the course of PRRS virus (PRRSV) infection is subclinical, laboratory diagnosis is necessary to detect the virus or specific antibodies. The aim of this study was to assess the sensitivity and specificity of IDEXX PRRS X3 Ab Test (IDEXX, USA), Civtest Suis E/S (Hipra, Spain), INgezim PRRS 2.0 (Ingenasa, Spain), VetExpert PRRS Ab ELISA 4.0 (BioNote, Korea), Pigtype PRRSV Ab (Qiagen, Germany) and PrioCHECK PRRSV Antibody ELISA (ThermoFisher, USA), using serum samples obtained from 5 conventional PRRSV-positive and 5 PRRSV-negative Polish pig farms. Specificity of ELISAs ranged from 94.2% (ThermoFisher) to 100% (IDEXX and Hipra). ThermoFisher ELISA had the highest detection rate and detected 67.2% samples from PRRSV-positive farms as positive but considering its low specificity some of the positive results may be incorrect. IDEXX ELISA considered as a reference detected 64.8% positive sera in PRRSV-positive farms. On the other hand Hipra Elisa identified only 51.8% of samples as positive. The diagnostic sensitivity of five ELISAs relative to IDEXX ranged from 80.3% (Hipra) to 96.3% (ThermoFisher). Our study showed significant differences in specificity and diagnostic sensitivity between the compared kits. The differences in the performance appeared to be practically negligible on farms where early infection with PRRSV occurred. However, on PRRSV-negative farms, or farms with PRRSV stable sow herds, some ELISAs can give results not reflecting the infection status in specific age groups.

The detection and genetic diversity of novel porcine parvovirus 7 (PPV7) on Polish pig farms.

In the last years several novel parvoviruses (PPVs) were discovered in pigs worldwide. The most recently discovered porcine parvovirus species is PPV7, which was detected in USA and China to date. This study reports the first evidence of PPV7 in Europe. Overall, 902 serum samples and 896 fecal samples were collected between 2014 and 2017 from 3 to 20 weeks old pigs from 14 conventional swine farms in Poland. PPV7 DNA was detected in samples from all examined farms. Overall, PPV7 was detected in 39,0% fecal pools and in 19,6% serum pools. No positive results were obtained from 3 to 6-week-old pigs. In growing pigs and fatteners the virus was detected in 26,1% serum pools and 51,4% fecal pools. PPV7 infection dynamics was similar in all tested farms. Five complete REP gene sequences of PPV7 from Poland were obtained. The identity of Polish sequences ranged from 94.3 to 96.7% and from 93.5 to 96.7% at the nucleotide and amino acid level, respectively. Their identity to previously discovered sequences from USA and China ranged from 93.9 to 95.0% and from 91.8 to 95.4% at the nucleotide and amino acid level, respectively.

Transcriptional profiles of PBMCs from pigs infected with three genetically diverse porcine reproductive and respiratory syndrome virus strains.

Porcine reproductive and respiratory syndrome virus is the cause of reproductive failure in sows and respiratory disease in young pigs, which has been considered as one of the most costly diseases to the worldwide pig industry for almost 30 years. This study used microarray-based transcriptomic analysis of PBMCs from experimentally infected pigs to explore the patterns of immune dysregulation after infection with two East European PRRSV strains from subtype 2 (BOR and ILI) in comparison to a Danish subtype 1 strain (DAN). Transcriptional profiles were determined at day 7 post infection in three tested groups of pigs and analysed in comparison with the expression profile of control group. Microarray analysis revealed differential regulation (> 1.5-fold change) of 4253 and 7335 genes in groups infected with BOR and ILI strains, respectively, and of 12518 genes in pigs infected with Danish strain. Subtype 2 PRRSV strains showed greater induction of many genes, especially those involved in innate immunity, such as interferon stimulated antiviral genes and inflammatory markers. Functional analysis of the microarray data revealed a significant up-regulation of genes involved in processes such as acute phase response, granulocyte and agranulocyte adhesion and diapedesis, as well as down-regulation of genes enrolled in pathways engaged in protein synthesis, cell division, as well as B and T cell signaling. This study provided an insight into the host response to three different PRRSV strains at a molecular level and demonstrated variability between strains of different pathogenicity level.

Pigs Lacking the Scavenger Receptor Cysteine-Rich Domain 5 of CD163 Are Resistant to Porcine Reproductive and Respiratory Syndrome Virus 1 Infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. CD163 protein is expressed at high levels on the surface of specific macrophage types, and a soluble form is circulating in blood. CD163 has been described as a fusion receptor for PRRSV, with the scavenger receptor cysteine-rich domain 5 (SRCR5) region having been shown to be the interaction site for the virus. As reported previously, we have generated pigs in which exon 7 of the CD163 gene has been deleted using CRISPR/Cas9 editing in pig zygotes. These pigs express CD163 protein lacking SRCR5 (ΔSRCR5 CD163) and show no adverse effects when maintained under standard husbandry conditions. Not only was ΔSRCR5 CD163 detected on the surface of macrophage subsets, but the secreted, soluble protein can also be detected in the serum of the edited pigs, as shown here by a porcine soluble CD163-specific enzyme-linked immunosorbent assay (ELISA). Previous results showed that primary macrophage cells from ΔSRCR5 CD163 animals are resistant to PRRSV-1 subtype 1, 2, and 3 as well as PRRSV-2 infection in vitro Here, ΔSRCR5 pigs were challenged with a highly virulent PRRSV-1 subtype 2 strain. In contrast to the wild-type control group, ΔSRCR5 pigs showed no signs of infection and no viremia or antibody response indicative of a productive infection. Histopathological analysis of lung and lymph node tissue showed no presence of virus-replicating cells in either tissue. This shows that ΔSRCR5 pigs are fully resistant to infection by the virus.IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) is the etiological agent of PRRS, causing late-term abortions, stillbirths, and respiratory disease in pigs, incurring major economic losses to the worldwide pig industry. The virus is highly mutagenic and can be divided into two species, PRRSV-1 and PRRSV-2, each containing several subtypes. Current control strategies mainly involve biosecurity measures, depopulation, and vaccination. Vaccines are at best only partially protective against infection with heterologous subtypes and sublineages, and modified live vaccines have frequently been reported to revert to virulence. Here, we demonstrate that a genetic-control approach results in complete resistance to PRRSV infection in vivo CD163 is edited so as to remove the viral interaction domain while maintaining protein expression and biological function, averting any potential adverse effect associated with protein knockout. This research demonstrates a genetic-control approach with potential benefits in animal welfare as well as to the pork industry.