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Use of the domestic Swine as an alternative animal model for conducting dermal irritation/corrosion studies on fatty amine ethoxylates.

The dermal irritation/corrosion potential of four fatty amine ethoxylates was evaluated using domestic swine as an alternative animal model. The weanling pig was chosen for this study due to the similarity of its skin to human skin with respect to structure and physiology. The four products, Armostat 310 (tallow bis (2-hydroxyethyl) amine), Armostat 410 (coco bis (2-hydroxyethyl) amine), Armostat 710 (oleyl bis (2-hydroxyethyl) amine), and Armostat 1800 (stearyl bis (2-hydroxyethyl) amine) were applied to the skin of three domestic swine for 4 hours in accordance with internationally accepted guidelines. Dermal reactions were scored up to 168 hours post application. Armostat 310, Armostat 410, and Armostat 710 were all classified as moderately irritating, whereas Armostat 1800 was nonirritating. None of the additives were corrosive to the skin of domestic swine. These products had been previously classified as corrosive based on studies conducted with rabbits using Armostat 310. This study demonstrates that the use of a more appropriate animal model will generate data that are relevant to humans for the classification of the potential dermal irritation and/or corrosive properties of chemicals.

Administration, Cutaneous↗

Airborne microbial contents in two types of swine confinement buildings in Quebec.

Airborne microorganisms were isolated with a sampler in two types of swine confinement buildings (farrowing units and fattening units). Respirable (particles less than 5 microns) and total dust fractions were obtained. Samplings were repeated every 2 weeks for a total of 6 samplings per unit between January and April. The predominant microorganisms isolated were bacteria (up to 1.25 x 10(6) CFU/m3) with an important fraction in the respirable size range (up to 0.5 x 10(6) CFU/m3). Only small quantities of gram-negative bacteria, yeasts, and molds were found. Identification of the colonies isolated revealed a great diversity of microorganisms present in the air of the different buildings. Enterobacter agglomerans, Moraxella, Acinetobacter calcoaceticus, and Pseudomonas were the most frequently identified bacteria. Scopulariopsis, Aspergillus, Penicillium, and Candida were the most numerous fungi. Faenia rectivirgula, the causative agent of farmer's lung, was not a major contaminant. The results show some differences in airborne microbial contamination between farrowing and fattening units; the distinction, however, is not clear-cut and was observed only for the total bacteria. The level of airborne microbial contamination in swine units does not significantly vary as a function of the outside temperature. Some species of bacteria and fungi isolated in this study are known to induce extrinsic allergic alveolitis. Other fungi are known to be potentially pathogenic for man. The air of swine confinement buildings is highly contaminated with bacteria, yeasts, and molds at a level up to 1200 time higher than so-called "normal air."

Air Microbiology↗

Generation and mapping of expressed sequence tags from virus-infected swine macrophages.

In an effort to identify genes that have a major effect on macrophage function during viral infection, we employed differential display reverse transcription (DDRT)-PCR to capture expressed sequence tags (ESTs) of swine alveolar macrophages infected by the porcine reproductive and respiratory syndrome virus (PRRSV). Sequence analyses showed that approximately 60% of these ESTs had significant similarity (> or =93%) to known pig ESTs or genes or matched sequences from other species with homology > or =80%. To determine chromosomal localization, PCR-based mapping was performed across either swine somatic cell hybrid or radiation hybrid panels. A total of 48 porcine viral response ESTs were mapped via the swine somatic cell panel or the INRA-Minnesota porcine Radiation Hybrid (IMpRH) panel (LOD > 6.0). Northern blot analyses confirmed PRRSV-induced altered transcript expression for several ESTs, including a 2'-5' oligoadenylate synthetase and a putative dual-specificity phosphatase. These virus-response ESTs represent good candidate genes for understanding PRRSV pathogenesis and for dissecting host genes which may have major effect on disease resistance.

2',5'-Oligoadenylate Synthetase↗

Changing viral susceptibility of a human cell line in continuous cultivation. I. Production of infective virus in a variant of the Chang conjunctival cell following infection with swine or N-WS influenza viruses.

During its serial transfer and cultivation in this laboratory, a human conjunctival cell line (Chang) was observed to change in morphology. Concurrently no change was noted in the susceptibility of the cells to viruses capable of infecting the original cell line. However, it was noted that the derived variant cell line had acquired susceptibility to the induction of cytopathic effects and incomplete virus formation by several strains of influenza viruses. It was then discovered that swine influenza virus and the N-WS strain of influenza A virus could be serially propagated in the derived cell line with production of infective virus. The swine virus required adaptation, but the N-WS strain did not. N-WS and swine influenza viruses multiply with infective virus formation only in the variant conjunctival cell and in no other cell line. Antigenic, cytologic, and virologic evidence is presented that the influenza virus-susceptible variant cell is of human origin and is not a contaminating cell exogenously introduced. Transition of a cell line from complete insusceptibility to susceptibility to virus infection and multiplication has not been described previously.

Animals↗

Cerebral perfusion pressure directed therapy following traumatic brain injury and hypotension in swine.

There is a paucity of studies, clinical and experimental, attesting to the benefit of cerebral perfusion pressure (CPP) directed pressor therapy following traumatic brain injury (TBI). The current study evaluates this therapy in a swine model of TBI and hypotension. Forty-five anesthetized and ventilated swine received TBI followed by a 45% blood volume bleed. After 1 h, all animals were resuscitated with 0.9% sodium chloride equal to three times the shed blood volume. The experimental group (PHE) received phenylephrine to maintain CPP > 80 mm Hg; the control group (SAL) did not. Outcomes in the first phase (n = 33) of the study were as follows: cerebro-venous oxygen saturation (S(cv)O(2)), cerebro-vascular carbon dioxide reactivity (DeltaS(cv)O(2)), and brain structural damage (beta-amyloid precursor protein [betaAPP] immunoreactivity). In the second phase (n = 12) of the study, extravascular blood free water (EVBFW) was measured in the brain and lung. After resuscitation, intracranial and mean arterial pressures were >15 and >80 mm Hg, respectively, in both groups. CPP declined to 64 +/- 5 mm Hg in the SAL group, despite fluid supplements. CPP was maintained at >80 mm Hg with pressors in the PHE group. PHE animals maintained better S(cv)O(2) (p < 0.05 at 180, 210, 240, 270, and 300 min post-TBI). At baseline, 5% CO(2) evoked a 16 +/- 4% increase in S(cv)O(2), indicating cerebral vasodilatation and luxury perfusion. By 240 min, this response was absent in SAL animals and preserved in PHE animals (p < 0.05). Brain EVBFW was higher in SAL animals; however, lung EVBFW was higher in PHE animals. There was no difference in betaAPP immunoreactivity between the SAL and PHE groups (p > 0.05). In this swine model of TBI and hypotension, CPP directed pressor therapy improved brain oxygenation and maintained cerebro-vascular CO(2) reactivity. Brain edema was lower, but lung edema was greater, suggesting a higher propensity for pulmonary complications.

Animals↗

Cloning and characterization of Swine interleukin-17, preferentially expressed in the intestines.

Interleukin-17 (IL-17), initially reported as CTLA-8, is a proinflammatory cytokine produced mainly by activated T cells. In the present study, the cDNA of a swine IL-17 (PoIL-17) gene was cloned from activated neonatal thymocytes, and the recombinant PoIL-17 (rPoIL-17) was biologically characterized. The complete open reading frame (ORF) of PoIL-17 contains 462-bp coding deduced 153 amino acid residues, with a calculated molecular weight of 17.3 kDa. The amino acid sequence showed 72.9%, 64.9%, 64.7%, 60.1%, and 47.4% similarities with that of human, rat, mouse, Herpesvirus saimiri ORF 13, and chicken, respectively. The six cysteine residues conserved over species including the virus were observed in PoIL-17. We successfully prepared the recombinant mature form of PoIL-17 and analyzed its biologic activities for swine splenocytes. RT-PCR analysis revealed a marked upregulation of expression of IL-1beta, IL-8, tumor necrosis factor-alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), and monocyte chemotactic protein-1 (MCP-1) mRNA expression in splenocytes treated with 100 ng/ml rPoIL-17 for 3 h. Furthermore, a swine chemokine, alveolar macrophage-derived neutrophil chemotactic factor II (AMCF-II), which was classified into the CXC subfamily was also augmented in mRNA level. This evidence indicates that recombinat PoIL-17 expressed in Escherichia coli was biologically active and exerted similar effects to those of a human (HuIL-17) and murine IL-17 (MuIL-17). The PoIL-17 mRNA is strongly expressed in the adult heart, skin, and, interestingly, intestinal tissues, including mesenteric lymph nodes but is restricted in neonatal tissues by using real-time quantitative RT-PCR. The gene sequence and biologically active recombinat protein for PoIL-17 will be useful for elucidation of the role of IL-17 in the regulation of intestinal immune responses.

Amino Acid Sequence↗

The effect of subtherapeutic chlortetracycline on antimicrobial resistance in the fecal flora of swine.

The aims of this research were to determine the association between inclusion of subtherapeutic chlortetracycline in the diets of swine and the prevalence and antimicrobial resistance of Salmonella; define the association between inclusion of subtherapeutic chlortetracycline and antimicrobial resistance in the aerobic Gram-negative fecal flora of swine; and estimate the proportion of total model variance attributable to farm, pig, and colony level effects. There was no association between subtherapeutic chlortetracycline exposure and Salmonella prevalence. There were increased odds for an aerobic Gram-negative fecal isolate to be resistant to ampicillin, ceftriaxone, and tetracycline if isolated from a pig that received chlortetracycline. There was a positive association between inclusion of subtherapeutic chlortetracycline in the diet and resistance to multiple antimicrobials. The proportion of total variance associated with farm, pig, and colony varied based on the resistance phenotype. Because farm-level variance contributed a small proportion to total variance in all models, effects of antimicrobial use interventions observed in this study may be predictive of anticipated impact of interventions on most swine farms. Resources for future investigations may be better allocated to sampling more pigs and more bacterial colonies per pig in relationship to the number of farms.

Animals↗

Recombinant fusion protein and DNA vaccines against foot and mouth disease virus infection in guinea pig and swine.

In this study, we provide evidence that a recombinant fusion protein containing beta-galactosidase and a tandem repeat peptide of immunogenic dominant epitope of foot-and-mouth disease virus (FMDV) VP1 protein elicits high levels of neutralizing antibody and protects both guinea pigs and swine against infection. Vaccination with this fusion protein induced a FMDV-specific proliferative T-cell response and a neutralizing antibody response. The immunized guinea pigs and swine were protected against FMD type O virus infection. Two DNA plasmids expressing genes of foot-and-mouth disease were constructed. Both plasmids pBO1 and pCO1 contain a signal sequence of the swine immunoglobulin G (IgG) gene and fusion protein gene of pXZ84. The signal sequence and fusion protein gene were under the control of a metallothionein promoter in the case of the pBO1 plasmid and under the control of a cytomegalovirus immediate early promoter in the case of pCO1 plasmid. When pBO1 and pCO1 were inoculated intramuscularly into guinea pigs, both plasmids elicited a neutralizing antibody response and spleen cell proliferation increased following stimulation with FMDV antigen, but animals were not protected from viral challenge.

Animals↗

Minimum alveolar concentration (MAC) of xenon in intubated swine.

BACKGROUND: The minimum alveolar concentration (MAC) is a traditional index of the hypnotic potency of an inhalational anaesthetic. To investigate the anaesthetic as well as the unwanted effects of xenon (Xe) in a swine model, it is useful to know MAC(Xe). METHODS: The study was performed using ten swine (weight 27.8-35.4 kg) anaesthetized with halothane and Xe 0, 15, 30, 40, 50 and 65% in oxygen. With each Xe concentration, various concentrations of halothane were administered in a step-by-step design. For each combination, a supramaximal pain stimulus (claw clamp) was applied and the appearance of a withdrawal reaction was recorded. The MAC(Xe) with halothane was calculated using a logistic regression model. RESULTS: During stable ventilation, haemodynamics and temperature, MAC(Xe) value was determined as 119 vol. % (95% confidence limits 103-135). CONCLUSION: MAC(Xe) in swine was calculated by extrapolation of a logistic regression model. Its theoretical value is 119 vol. %.

Anesthesia, Closed-Circuit↗

Mycobacterium avium-intracellulare complex serovars isolated in South Africa from humans, swine, and the environment.

From 1968 to 1978 a total of 792 strains of the Mycobacterium avium-intracellulare complex were isolated from various sources in South Africa and serotyped according to Schaefer's seroagglutination test' 569 strains were from healthy rural persons, 171 strains were from lymph node lesions of swine, and 52 environmental strains were from animal feed and bedding, plants, dust, and soil. Serotyping was undertaken to determine the exposure of humans and animals to various serovars, to ascertain the predominance of individual serovars from the various sources, and to pinpoint, if possible, reservoirs of infection. Occurrence of M. avium serovars 1--3 was low in all sources studied: 1% in humans, 4% in the environment, and 14% in swine. The predominant human serovars were 7, 14, 19, 24, and 13, whereas the predominant swine serovars were 8, 4, double type 4/8, and 10. Serovars found in the environment were 9, 10, 13, 14, 16, and 17, with serovars 4 and 8 predominating.. Therefore, in South Africa, as in Australia, humans and animals are continuously exposed to various serovars, particularly serovars 4--24, which can be frequently and regularly isolated from the environment, the possible source of infection.

Animal Feed↗

Transmural coronary vasodilator reserve, and flow distribution during tachycardia in conscious young swine with right ventricular hypertrophy.

Regional distribution of myocardial blood flow (MBF) was examined in eight normal and nine pulmonary artery banded (PAB) pigs before and during pacing induced tachycardia (heart rates: 175, 225 and 275 beats X min-1) as well as during iv adenosine infusion (1.5 mg X kg-1 X min-1; maximal coronary vasodilatation) using radionuclide labelled 15 micron diameter microspheres that were injected into the left atrium. It was observed that MBF per unit myocardial mass in the hypertrophied right ventricle (RV) of PAB pigs was similar to that in the RV of normal pigs. Also, minimal coronary vascular resistance per unit myocardial mass was similar between the two groups of pigs for RV as well as left ventricle (LV). This suggests that the increase in RV myocardial mass of young PAB swine was attended by appropriate adjustments in functional cross-sectional area of the RV coronary vascular bed. Despite similarity of maximal coronary vasodilator capacity in the two groups of swine, during pacing induced tachycardia MBF in the hypertrophied RV subendocardium as well as the right and middle layers of the interventricular septum in PAB pigs increased to a significantly lower level than in normal pigs and the RV endo:epi perfusion ratio, unlike in normal pigs, decreased to near unity. Increments in transmural LV MBF of PAB pigs were also attenuated during pacing at 225 and 275 beats X min-1 but the LV endo:epi perfusion ratio for the two groups of pigs remained similar. These findings suggest a possible overall depression of myocardial function in PAB swine.

Adenosine↗

Importance of vasomotor tone to myocardial function and regional metabolism during constant flow ischaemia in swine.

STUDY OBJECTIVE: The aim was to test the hypothesis that the release of vascular tone with adenosine during constant flow ischaemia alters both transmural function and regional metabolism in a detrimental way. DESIGN: In one group of anaesthetised swine, the effects of graded reductions of flow on segmental left ventricular function, myocardial oxygen consumption (MVO2), and lactate production in the distribution of the left anterior descending coronary artery (LAD) were determined. In a second group, a model of constant flow ischaemia was induced to test how altering vascular tone with adenosine changed the relationship of flow, function, and metabolism. EXPERIMENTAL MATERIAL: The experiments were performed in 20 open chest, anaesthetised swine. Protocol A consisted of 11 animals and protocol B of nine animals. MEASUREMENTS AND MAIN RESULTS: In protocol A, during graded ischaemia, reductions in flow, % systolic wall thickening (WTh), normalised MVO2 and % lactate extraction (%LE) correlated well with reductions in coronary perfusion pressure when fitted with 3rd order polynominal curves (r = 0.78, 0.87, 0.85 and 0.81 respectively; p less than 0.00001). In protocol B, during constant flow ischaemia, at control, % WTh was 33 (SD 11)%, mean coronary artery pressure was 72(10) mm Hg, mean LAD transmural flow was 0.99(0.43) ml.min-1.g-1, and % LE was +14(9)%. With inflation of a hydraulic occluder on the LAD, perfusion pressure was lowered to 38(5) mm Hg and transmural flow dropped to 0.76(0.31) ml.min-1.g-1 (intact vasomotion). During an infusion of intracoronary adenosine with flow held constant (absent vasomotion), %WTh was further reduced from 27(9) to 13(10) (p less than 0.001), and %LE from -18(42) to -70(61) (p less than 0.05). MVO2 with and without vasomotion did not differ significantly at 3.14(0.75) and 3.18(0.86) ml.min-1.g-1 respectively. CONCLUSION: In swine coronary circulation, reductions in regional function, MVO2 and lactate production correlate well with reductions in flow and perfusion pressure during ischaemia with vasomotor tone intact. The effect of adenosine on vascular tone during constant flow ischaemia caused dramatic reductions in function and lactate extraction without altering MVO2. This emphasises the important role of vascular tone in protecting both transmural function and regional metabolism during moderate ischaemia.

Adenosine↗

Antigenic relationship between human coronavirus strain OC 43 and hemagglutinating encephalomyelitis virus strain 67N of swine: antibody responses in human and animal sera.

Hemagglutinating encephalomyelitis virus of swine (HEV) was adapted to growth in suckling mouse brain. Electron micrographs of HEV-infected suckling mouse brain, prepared by negative staining and thin-section techniques, exhibited typical morphological characteristics shared with other members of the Coronaviridae. The adaptation of HEV to suckling mouse brain facilitated serologic testing by the use of common host reagents and compatible animal systems. With hemagglutination inhibition, complement-fixation, and neutralization tests, an antigenic relationship was demonstrated between human coronavirus OC 43 and HEV in specific immune and hyperimmune animal sera. Children and adults with seroconversion to OC 43 antigen had diagnostic rises in titer of antibody to HEV antigens. Individuals with seroconversion to human coronaviruse 229E and B814 demonstrated antibody to HEV but not diagnostic rises in titer. Swine with titers of antibody to HEV had lower or no detectable titers of antibody to coronavirus OC 43. Although the prevalence and geometric mean titer of antibody to OC 43 were higher than the titer of antibody to HEV in every group of normal humans tested, significant differences in antibody response to coronavirus OC 43 and HEV were seen between populations that did or did not have possible contact with swine. The evidence suggested that antibody to HEV in humans probably represented a heterologous response to infection with coronavirus OC 43. However, a heterotypic response to unknown or uncharacterized strains of coronavirus cannot be excluded.

Adult↗

Effects of morphine dependence on the pathogenesis of swine herpesvirus infection.

To further understand the effects of opiates on the pathogenesis of infectious disease, naturally occurring pathogens were studied in a swine model. Swine were given morphine for 21-42 days to establish a tolerant, dependent state. On day 7 after morphine initiation, pigs were challenged with swine herpesvirus-1 (SHV-1); on day 14, selected animals were superinfected with Pasteurella multocida. Evaluations were made of the clinical disease, protective effect of SHV-1 vaccination, and pathology. Morphine-dependent animals developed significantly greater virus-induced and secondary bacterial pneumonia. Prior vaccination with SHV-1 was not protective against pneumonia in morphine-dependent pigs. Unexpectedly, clinical signs associated with neurologic disease were less pronounced, and mortality from viral encephalitis was decreased in morphine-treated animals. Collectively, the findings demonstrate that morphine dependence is associated with a marked alteration of the pathogenesis of SHV-1 and that the effects of this opiate on pathogenesis are determined by the specific site of infection.

Animals↗

The swine Ig heavy chain locus has a single JH and no identifiable IgD.

Sequence analysis of 84 V region cDNAs expressed with IgM, IgG and IgA from both adult and newborn swine suggested that their JH segments had been derived from the same germline JH. Only a single hybridizing JH segment could be identified in genomic DNA, in a JH-C mu cosmid and in a Sacl fragment of the cosmid extending 5 kb 5' of the EnhH. The single germline JH segment mapped 6 kb 5' to C mu. This JH had a sequence identical to 40 of 42 JH segments expressed in a newborn piglet and 25 of 42 expressed by adult swine. None of the 19 JH segments which varied from the germline sequence were identical to each other and half of the nucleotide changes were silent. No cosmid DNA hybridizing with heterologous probes for C delta could be found within 20 kb 3' of C mu and C delta could not be cloned from genomic or cDNA libraries. A conserved IgD fragment could be amplified from human, mouse and rat genomic DNA but not from rabbit, swine or cattle. We hypothesize that heavy chain organization and constituency in homeothermic vertebrates is correlated with the site of secondary antibody repertoire development and the mechanism(s) used.

Animals↗

Iron and folate utilization in reproducing swine and their progeny.

The purpose of this investigation was to assess the usefulness of maternal and neonatal swine as animal models for studying iron (Fe) and folate nutrition during reproduction and growth. Sows (n = 18) were fed a purified diet containing 0.6 mg folate/kg diet and either 25 (Fe-) or 125 (Fe+) mg iron/kg diet throughout gestation and lactation. Litters were culled to eight on d 2 of lactation and four piglets/litter were given an intramuscular injection of iron dextran (100 mg/kg body wt). Plasma and red blood cell folate concentrations among all sows decreased (greater than 50%) after conception (P less than 0.001). Plasma folate concentration of Fe- sows was 47% and 69% of Fe+ sows on d 7 and 21 of lactation, respectively (P less than 0.05). All sows secreted milk that contained low levels of folate (12-36 nmol/l) and was devoid of long-chain folylpolyglutamates. While mean milk folate concentration significantly decreased after d 1 of lactation among Fe- sows, no such decrease was observed in milk from Fe+ sows (P less than 0.05). Liver folate concentration was significantly reduced in piglets nursed by Fe- sows and given intramuscular iron dextran. It is concluded that there is an increased dietary requirement for folate and iron during reproduction in swine, and that current recommended amounts of folate (0.6 mg/kg diet) and iron (80 mg/kg diet) may be underestimates of requirements for reproduction. Further, results show that iron nutrition may alter folate utilization in maternal and neonatal swine.

Anemia, Hypochromic↗

Novel tocotrienols of rice bran suppress cholesterogenesis in hereditary hypercholesterolemic swine.

A tocotrienol-rich fraction (TRF(25)) and novel tocotrienols (d-P(21)-T3 and d-P(25)-T3) of rice bran significantly lowered serum and low density lipoprotein cholesterol levels in chickens. The present study evaluated the effects of novel tocotrienols on lipid metabolism in swine expressing hereditary hypercholesterolemia. Fifteen 4-mo-old genetically hypercholesterolemic swine were divided into five groups (n = 3). Four groups were fed a corn-soybean control diet, supplemented with 50 microg of either TRF(25), gamma-tocotrienol, d-P(21)-T3 or d-P(25)-T3 per g for 6 wk. Group 5 was fed the control diet for 6 wk and served as a control. After 6 wk, serum total cholesterol was reduced 32-38%, low density lipoprotein cholesterol was reduced 35-43%, apolipoprotein B was reduced 20-28%, platelet factor 4 was reduced 12-24%, thromboxane B(2) was reduced 11-18%, glucose was reduced 22-25% (P<0.01), triglycerides were reduced 15-19% and glucagon was reduced 11-17% (P<0.05) in the treatment groups relative to the control. Insulin was 100% greater (P<0.01) in the treatment groups than in the control group. Preliminary data (n = 1) indicated that hepatic activity of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase was lower in the treatment groups, and cholesterol 7alpha-hydroxylase activity was unaffected. Cholesterol and fatty acid levels in various tissues were lower in the treatment groups than in control. After being fed the tocotrienol-supplemented diets, two swine in each group were transferred to the control diet for 10 wk. The lower concentrations of serum lipids in these four treatment groups persisted for 10 wk. This persistent effect may have resulted from the high tocotrienol levels in blood of the treatment groups, suggesting that the conversion of tocotrienols to tocopherols may not be as rapid as was reported in chickens and humans.

Animals↗

Hairpin loop structure of African swine fever virus DNA.

The ends of African swine fever virus genome are formed by a 37 nucleotide-long hairpin loop composed, almost entirely, of incompletely paired A and T residues. The loops at each DNA end were present in two equimolar forms that, when compared in opposite polarities, were inverted and complementary (flip-flop), as in the case of poxvirus DNA. The hairpin loops of African swine fever and vaccinia virus DNAs had no homology, but both DNAs had a 16 nucleotide-long sequence, close to the hairpin loops, with an homology of about 80%. An analysis of African swine fever virus replicating DNA showed head-to-head and tail-to-tail linked molecules that may be replicative intermediates.

African Swine Fever Virus↗