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Swine are increasingly studied as animal models of human disease. The anatomy, size, longevity, physiology, immune system, and metabolism of swine are more like humans than traditional rodent models. In addition, the size of swine is preferred for surgical placement and testing of medical devices destined for humans. These features make swine useful for biomedical, pharmacological, and toxicological research. With recent advances in gene-editing technologies, genetic modifications can readily and efficiently be made in swine to study genetic disorders. In addition, gene-edited swine tissues are necessary for studies testing and validating xenotransplantation into humans to meet the critical shortfall of viable organs versus need. Underlying all of these biomedical applications, the knowledge of husbandry, background diseases and lesions, and biosecurity needs are important for productive, efficient, and reproducible research when using swine as a human disease model for basic research, preclinical testing, and translational studies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Porcine epidemic diarrhea virus (PEDV) infection leads to diarrhea and subsequently to decreased feed efficiency and growth in weaned pigs. Given that few studies have addressed the host-virus interaction in vivo, this study focused on endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in jejunal epithelial cells during PEDV infection. Eight-week-old pigs ( n = 64) were orally inoculated with PEDV IN19338 strain ( n = 40) or sham-inoculated ( n = 24) and analyzed for PEDV viral RNA shedding using reverse transcription-quantitative polymerase chain reaction and for viral antigen within enterocytes using immunohistochemistry (IHC). ER stress was analyzed in a subset of 9 PEDV-inoculated pigs with diarrhea, detectable viral RNA, and viral antigen (PEDV-immunopositive pigs). Compared with control pigs, PEDV-immunopositive pigs had a reduced ratio of villus height to crypt depth in the jejunum ( P = .002, n = 9 per group), consistent with intestinal injury. The protein levels of ATF6, IRE1, PERK, XBP1u, ATF4, GRP78, and caspase-3 were assessed in jejunal epithelial cells at the villus tips via IHC. Both ER stress and UPR were demonstrated in PEDV-immunopositive pigs by the increased expression of ATF6 ( P = .047), IRE1 ( P = .007), and ATF4 ( P = .001). The expression of GRP78 ( P = .024) and caspase-3 ( P = .004) were also increased, indicating an accompanying increase in ER protein folding capacity and apoptosis. Overall, these results reveal that PEDV infection induces ER stress and UPR in intestinal epithelial cells of weaned pigs.

In the small intestine, localized innate mucosal immunity is critical for intestinal homeostasis. Porcine epidemic diarrhea virus (PEDV) infection induces villus injury and impairs digestive function. Moreover, the infection might comprise localized innate mucosal immunity. This study investigated specific enterocyte subtypes and innate immune components of weaned pigs during PEDV infection. Four-week-old pigs were orally inoculated with PEDV IN19338 strain (n = 40) or sham-inoculated (n = 24). At day post inoculation (DPI) 2, 4, and 6, lysozyme expression in Paneth cells, cellular density of villous and Peyer's patch microfold (M) cells, and the expression of polymeric immunoglobulin receptor (pIgR) were assessed in the jejunum and ileum by immunohistochemistry, and interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured in the jejunum by ELISA. PEDV infection led to a decrease in the ratios of villus height to crypt depth (VH-CD) in jejunum at DPI 2, 4, and 6 and in ileum at DPI 4. The number of villous M cells was reduced in jejunum at DPI 4 and 6 and in ileum at DPI 6, while the number of Peyer's patch M cells in ileum increased at DPI 2 and then decreased at DPI 6. PEDV-infected pigs also had reduced lysozyme expression in ileal Paneth cells at DPI 2 and increased ileal pIgR expression at DPI 4. There were no significant changes in IL-1β and TNF-α expression in PEDV-infected pigs compared to controls. In conclusion, PEDV infection affected innate mucosal immunity of weaned pigs through alterations in Paneth cells, villous and Peyer's patch M cells, and pIgR expression.

In the past decade, different members of the genus Mamastrovirus have been associated with outbreaks of neurologic disease in humans, cattle, sheep, mink, and, most recently, porcine astrovirus 3 (PoAstV3) in swine. We performed a retrospective analysis of 50 cases of porcine neurologic disease of undetermined cause but with microscopic lesions compatible with a viral encephalomyelitis to better understand the role and pathogenesis of PoAstV3 infection. Nucleic acid was extracted from formalin-fixed paraffin-embedded (FFPE) tissue for reverse transcription quantitative polymerase chain reaction (RT-qPCR) testing for PoAstV3. In addition, 3 cases with confirmed PoAstV3-associated disease were assayed by RT-qPCR to investigate PoAstV3 tissue distribution. PoAstV3 was detected in central nervous system (CNS) tissue via RT-qPCR and in situ hybridization in 13 of 50 (26%) FFPE cases assayed. PoAstV3 was rarely detected in any tissues outside the CNS. Positive cases from the retrospective study included pigs in various production categories beginning in 2010, the earliest year samples were available. Based on these results, PoAstV3 appears to be a recurring putative cause of viral encephalomyelitis in swine that is rarely detected outside of the CNS at the time of clinical neurologic disease, unlike other common viral causes of neurologic disease in swine.

Swine dysentery is a severe enteric disease in pigs, which is characterized by bloody to mucoid diarrhea and associated with reduced growth performance and variable mortality. This disease is most often observed in grower-finisher pigs, wherein susceptible pigs develop a significant mucohemorrhagic typhlocolitis following infection with strongly hemolytic spirochetes of the genus Brachyspira. While swine dysentery is endemic in many parts of the world, the disease had essentially disappeared in much of the United States by the mid-1990s as a result of industry consolidation and effective treatment, control, and elimination methods. However, since 2007, there has been a reported increase in laboratory diagnosis of swine dysentery in parts of North America along with the detection of novel pathogenic Brachyspira spp worldwide. Accordingly, there has been a renewed interest in swine dysentery and Brachyspira spp infections in pigs, particularly in areas where the disease was previously eliminated. This review provides an overview of knowledge on the etiology, pathogenesis, and diagnosis of swine dysentery, with insights into risk factors and control.

Porcine epidemic diarrhea virus (PEDV) was first recognized in North America in April 2013 and has since caused devastating disease. The objective of this study was to characterize disease and viral detection associated with an original North American PEDV isolate inoculated in neonatal piglets. Thirty-six 1-day-old cesarean-derived and colostrum-deprived piglets were randomly assigned to the control (n = 16) or challenged group (n = 20); the latter were orogastrically inoculated with 1 ml of US/Iowa/18984/2013 PEDV isolate titered at 1 × 10(3) plaque-forming units per milliliter. Rectal swabs were collected from all piglets prior to inoculation and every 12 hours postinoculation (hpi) thereafter, with 4 control and 5 challenged piglets euthanized at 12, 24, 48, and 72 hpi. One piglet had a positive real-time quantitative polymerase chain reaction test on rectal swab at 12 hpi, and all remaining piglets were positive thereafter, with highest viral quantities detected at 24 and 36 hpi. Diarrhea was evident in 30% and 100% of challenged piglets at 18 and 24 hpi, respectively. Viral antigen was detected in enterocytes by immunohistochemistry in the duodenum and ileum of piglets euthanized at 12 hpi and was apparent throughout the small intestine of all piglets thereafter, with villus height:crypt depth ratios consistently below 4:1. Viremia was confirmed in 18 of 20 pigs at euthanasia. Clinical disease was severe and developed rapidly following infection with an original North American PEDV isolate, with lesions, viremia, and antigen detection possible by 12 hpi., (© The Author(s) 2015.)

Melanosis coli is a dark discoloration of the colon due to accumulation of pigment-laden macrophages in the lamina propria. Three case submissions were received where rectal discoloration was reported at slaughter in pigs from separate production systems and melanosis coli was confirmed microscopically. Tissues from affected and unaffected cohort pigs were evaluated for evidence of oxidative damage using immunohistochemical staining for 3-nitrotyrosine, 4-hyroxynonenol, and malondialdehyde. Affected colons had significantly greater immunolabeling for all 3 target compounds than unaffected colons (P ≤ .001, all analyses). Hepatic vitamin E levels were low in both affected and unaffected pigs, and there was a trend toward lower values in affected pigs. Given the limited number of slaughter-collected samples available for this investigation, further study is warranted to elucidate the possible association between low vitamin E concentrations and oxidative damage in cases of melanosis coli in pigs., (© The Author(s) 2014.)

Swine dysentery is classically associated with infection by Brachyspira hyodysenteriae, the only current officially recognized Brachyspira sp. that consistently imparts strong beta-hemolysis on blood agar. Recently, several strongly beta-hemolytic Brachyspira have been isolated from swine with clinical dysentery that are not identified as B. hyodysenteriae by PCR including the recently proposed species "Brachyspira hampsonii." In this study, 6-week-old pigs were inoculated with either a clinical isolate of "B. hampsonii" (EB107; n = 10) clade II or a classic strain of B. hyodysenteriae (B204; n = 10) to compare gross and microscopic lesions and alterations in colonic mucin expression in pigs with clinical disease versus controls (n = 6). Gross lesions were similar between infected groups. No histologic difference was observed between infected groups with regard to neutrophilic inflammation, colonic crypt depth, mucosal ulceration, or hemorrhage. Histochemical and immunohistochemical evaluation of the apex of the spiral colon revealed decreased expression of sulphated mucins, decreased expression of MUC4, and increased expression of MUC5AC in diseased pigs compared to controls. No difference was observed between diseased pigs in inoculated groups. This study reveals significant alterations in colonic mucin expression in pigs with acute swine dysentery and further reveals that these and other microscopic changes are similar following infection with "B. hampsonii" clade II or B. hyodysenteriae., (© The Author(s) 2014.)

Two cases of feline thymoma with amyloid deposition were encountered between 1982 and 2010. Neoplastic cells were separated by abundant, pale eosinophilic, homogeneous material that was congophilic and birefringent. Ultrastructurally, the neoplastic cells were connected by desmosomes, and the extracellular deposits were composed of nonbranching, hollow-cored fibrils, 8-10 nm in diameter. In the case with sufficient archived tissue for additional sections, the amyloid remained congophilic following potassium permanganate incubation, and the neoplastic cells were immunoreactive for pancytokeratin. The histologic, histochemical, ultrastructural, and immunohistochemical features of both neoplasms are consistent with epithelial-predominant thymoma with the unusual feature of intratumoral amyloid deposition. The affinity of the amyloid for Congo red following potassium permanganate incubation is consistent with non-AA amyloid. The ultrastructural findings were consistent with amyloid production by the neoplastic epithelial cells.

The pregnant guinea pig is an effective model for studying abortifacient Campylobacter spp, and previous experiments have demonstrated that C. jejuni IA3902 has a marked predilection for the subplacenta while sparing the placental disc in this species. In the study described here, the growth and chemotaxis of IA3902 and a reference strain (NCTC 11168) are compared in the presence of subplacental and placental factors, as well as bile and plasma, from pregnant and nonpregnant guinea pigs. Both strains grew better in subplacental versus placental disc tissue extracts at 24 hours; however, only IA3902 maintained this enhancement at 48 hours. Histochemistry and lectin histochemistry were used to localize mucin, iron, and l-fucose within the placental unit. Mucin was most abundant in subplacental lacunae, the junctional zone, and visceral yolk sac placenta, while iron was most abundant in the placental disc, and L-fucose-containing surface glycans were limited to the visceral yolk sac placenta. These 3 individual factors, along with progesterone and estradiol, were evaluated for effects on growth and chemotaxis of C. jejuni. Mucin, iron, and L-fucose were growth promoting, while l-fucose was also chemoattractive for both strains. Progesterone, estradiol, and pregnant guinea pig plasma did not affect growth or chemotaxis, and no difference was observed when bile from pregnant and nonpregnant animals was compared. These findings demonstrate the presence of specific factors within the guinea pig placental unit that drive chemotaxis and enhance growth of C. jejuni, shedding light on potential mechanisms underlying the fetoplacental tropism observed with this strain.

Toll-like receptors 2 and 4 (TLR2 and TLR4) are well-characterized cell surface receptors that recognize specific pathogen-associated molecular patterns and play an important role in pathogen recognition and activation of the innate immune system. Variable expression of TLR2 and TLR4 has been described in trophoblasts from normal and diseased placentas; yet, there are limited data regarding trophoblast TLR expression in response to specific placental pathogens, and TLR expression in the guinea pig placenta has not been described. The guinea pig is an effective model for Campylobacter-induced abortion of small ruminants, and the authors have shown by immunohistochemistry that C jejuni localizes within syncytiotrophoblasts of the guinea pig subplacenta. The present study was designed to determine if the expression of either TLR2 or TLR4 would be affected in subplacental trophoblasts following infection with C jejuni. Immunohistochemistry for TLR2 and TLR4 was performed on placenta from guinea pigs that aborted following inoculation with C jejuni and from sham-inoculated controls. Quantitative assessment of TLR expression was performed, and mean immunoreactivity for TLR2 was significantly higher in subplacental trophoblasts from animals that aborted compared with uninfected controls (P = .0283), whereas TLR4 expression was not statistically different (P = .5909). These results suggest that abortion in guinea pigs following infection with C jejuni is associated with increased TLR2 expression in subplacental trophoblasts and may reveal a possible role for TLR2 in the pathogenesis of Campylobacter-induced abortion.