Pseudorabies virus induces a rapid up-regulation of nitric oxide synthases in the nervous system of swine

Nitric oxide (NO) is a free radical gas with important roles in the host's immune response against viral infections. In this study, we examined the kinetics and distribution of nitric oxide synthase (NOS) expression during the early steps of infection of the porcine nervous system by the alphaherpesvirus pseudorabies virus (PRV). To this end, we examined changes in the expression of the three major NOS isoforms, neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS), by immunohistochemistry in the trigeminal ganglia and brain of pigs inoculated intranasally with a virulent PRV strain. The results obtained show that infection of the porcine nervous system by PRV induced a rapid and progressive increment in NOS expression that coincided in timing, location, and magnitude with those of virus propagation in the nervous tissue. A major finding of this study was that PRV caused not only nNOS and iNOS induction in a variety of cell types, but also eNOS up-regulation in endothelial cells and neurons; therefore, all possible sources of NO are activated and probably contribute to the overproduction of NO during infection with the neurotropic alphaherpesvirus PRV in its natural host.     

Nonsuppurative meningoencephalitis associated with Aleutian mink disease parvovirus infection in ranch mink.

Severe nonsuppurative meningoencephalitis associated with Aleutian mink disease parvovirus (ADV) infection was observed in adult ranch mink. Brain lesions included severe, locally extensive to coalescing lymphoplasmacytic meningoencephalitis with accompanying gliosis, satellitosis, and mild extension of inflammation into the leptomeninges. ADV was identified in mesenteric lymph node, spleen, brain, and liver of affected mink by polymerase chain reaction techniques. Sequences of the ADV isolate (TH5) revealed 2 unique residues in the region of the viral genome that determines pathogenicity. These findings suggest that certain strains of ADV may preferentially cause disease in the nervous system. ADV infection should be considered in the differential diagnosis of neurologic disorders in mink.     

Research Progress on Pseudorabies and Its Influence on Fur-bearing Animals

Pseudorabies outbreak and spread both at home and abroad since 2010.It is reported that some vaccinated swine are infected with pseudorabies virus,even a certain amount of death happened in not only China but European and American area.From about 7% in 2010 to 26% in 2014,the prevalence of field strain pseudorabies virus(PRV) rose year by year.At the same time,in the Northeast and North China including Shangdong province,fur-bearing animals as mink and fox also were attacked by this virus with a high virus carried rate reaching 30.6% to 37.2%.In addition,the PRV adapt to fur-bearing animals would cause high incidence and mortality rates.In order to study the causes of the disease and develop the prevention and control measures in time,pseudorabies epidemical situation,test method,the use of vaccine were reviewed in this paper.What's more,the endemism of the mink was expounded,and gave analysis and prospects to prevention as well as treatment of this disease on fur-bearing animals.     

伪狂犬病及其对毛皮动物的影响研究进展

自2010年以来,伪狂犬病在国内外呈暴发和蔓延趋势。免疫后猪感染伪狂犬现象在欧美地区和中国多数省份都有报道,且有一定数量的死亡发生。伪狂犬病野毒感染的血清阳性率逐年上升,从2010年的7%左右上升到2014年的26%。同时中国东北、华北和山东一带还有不同程度的水貂、狐狸等毛皮动物感染发病的情况,通过血清学和分子生物学检测发现阳性带毒率高达30.6%～37.2%。另外,适应了毛皮动物的伪狂犬病病毒会引起毛皮动物迅速发病和较高的死亡率。为了更好地研究该病发生的原因并及时地制定防控措施,作者对目前伪狂犬病在国内外的流行情况、疫苗的使用种类和该病的检测方法等方面进行了综合、系统的概括,并总结了在毛皮动物上发病的特有现象,就该病如何在毛皮动物中进行有效的治疗和防控做出了具体的分析和展望。     

Effect of infectious dose and season on development of hemorrhagic pneumonia in mink caused by Pseudomonas aeruginosa

Hemorrhagic pneumonia is an acute and fatal disease of farmed mink caused by Pseudomonas aeruginosa. The pathogenesis of this disease has not yet been resolved. Mink are the only animals known to be susceptible to acute, contagious, and fatal lung infections caused by P. aeruginosa. The purpose of this study was to investigate the correlation between dose-response and season of infection and to clarify whether Danish mink are carriers of P. aeruginosa on their nasal mucosa during the season for hemorrhagic pneumonia. To elucidate the pathogenesis of the disease, an infectious dose-response trial was carried out on adult mink and mink kits, both in the season for hemorrhagic pneumonia (November) as well as out of season (July). It proved difficult to infect mink via the intra-nasal route. Only 4 out of 60 infected mink developed clinical disease and were euthanized, all of them in November, illustrating that predisposing factors in the mink itself and not infectious dose might be crucial for disease development. We were able to culture P. aeruginosa from the nasal cavity of the clinically healthy experimental mink 8 d after inoculation. This indicated that the mink can carry P. aeruginosa on their nasal mucosa without developing the disease. It was not possible, however, to culture P. aeruginosa from the nasal cavity of clinically healthy mink obtained from farms in November, which indicates that the organism is not a normal part of the nasal mucosal flora of mink.     

Studies on influenza viruses H10N4 and H10N7 of avian origin in mink

An influenza A virus, A/mink/Sweden/84 (H10N4), was isolated from farmed mink during an outbreak of respiratory disease, histopathologically characterised by severe interstitial pneumonia. The virus was shown to be of recent avian origin and closely related to concomitantly circulating avian influenza virus. Serological investigations were used to link the isolated virus to the herds involved in the disease outbreak. Experimental infection of adult mink with the virus isolate from the disease outbreak reproduced the disease signs and pathological lesions observed in the field cases. The mink influenza virus also induced an antibody response and spread between mink by contact. The same pathogenesis in mink was observed for two avian influenza viruses of the H10N4 subtype, circulating in the avian population. When mink were infected with the prototype avian H10 influenza virus, A/chicken/Germany/N/49, H10N7, the animals responded with antibody production and mild pulmonary lesions but neither disease signs nor contact infections were observed. Detailed studies, including demonstration of viral antigen in situ by immunohistochemistry, of the sequential development of pathological lesions in the mink airways after aerosol exposure to H10N4 or H10N7 revealed that the infections progress very similarly during the first 24h, but are distinctly different at later stages. The conclusion drawn is that A/mink/Sweden/84, but not A/chicken/Germany/N/49, produces a multiple-cycle replication in mink airways. Since the viral distribution and pathological lesions are very similar during the initial stages of infection we suggest that the two viruses differ in their abilities to replicate and spread within the mink tissues, but that their capacities for viral adherence and entry into mink epithelial cells are comparable.     

Nonsuppurative meningoencephalomyelitis of unknown etiology in mink

A central nervous system disease of mink occurred in three unrelated fur farms in Oregon in September, 1981. Only kits four to five months old were affected. Clinical signs consisted of posterior ataxia progressing to complete posterior paralysis with loss of motor control and sensation. Complete or partial recovery occurred in approximately 1.5 months in most mink. Microscopic lesions consisted of severe nonsuppurative meningoencephalitis and meningomyelitis with vacuolation of the white matter of the brain and spinal cord. Canine distemper virus infection and other recognized causes were ruled out on the basis of clinical signs, history, lesions, or laboratory findings. Experimental inoculations of mink with brain and spinal cord specimens from affected mink failed to reproduce the disease.     

Comparison of virus isolation, immunofluorescence and DNA probe hybridization for detection of pseudorabies virus in experimentally infected pigs.

Virus isolation, immunofluorescent staining and DNA probe hybridization, three techniques for the detection of pseudorabies virus (PRV) have been compared in pigs experimentally infected with the Thailand CB-1 strain PRV. The virus isolation and DNA hybridization detection demonstrated a good correlation in detecting infection in live animals by nasal swabbing. In white blood cells an earlier detection was seen with the DNA-hybridization techniques. Consistent results with all the three techniques tested were found in organ materials as nasal mucosa and tonsils as well as in the olfactory bulb.     

猪伪狂犬病病毒潜伏感染检测方法研究进展

猪伪狂犬病是由伪狂犬病病毒引起的 ,是以仔猪的发病死亡和怀孕母猪繁殖障碍为特征的猪病 ,是危害养猪业的重要疫病之一。该病在世界上分布广泛 ,并有不断蔓延扩大的趋势。任何年龄的猪在耐过伪狂犬病病毒急性感染后均能形成潜伏感染 ,并可在体内终生潜伏 ,且不表现临床症状 ,在一定条件下 ,潜伏状态的病毒能被激活 ,引起复发性感染并向外散毒。这种伪狂犬病病毒潜伏 -激活循环机制决定了伪狂犬病病毒在猪群中的永远存在。猪一旦感染必须视为伪狂犬病病毒散播的潜在来源。因而对潜伏感染猪的剔除对于根除伪狂犬病病毒感染具有重要意义。国内外对潜伏感染的检测方法主要有鉴别血清学诊断、潜伏病毒的激活与检测、组织块培养技术、核酸探针技术以及PCR技术。本文主要综述了这几种方法的研究情况 ,并比较了其优缺点     

Investigation on the Production Performance of gE Antibody Positive Sows in Pig Farms Infected with Wild Type Pseudorabies Virus

Pseudorabies (PR) is caused by the Pseudorabies virus (PRV). It is an acute and hot highly contagious disease infecting livestock and a wide range of wild animals. In order to investigate the relationship between latent infection of Pseudorabies virus and sow production performance,this study collected production parameters of first-parity sows with wild virus gE positive and negtive in a Pseudorabies positive stable intensive farm, including total litter size, healthy litter size, weak litter size, stillbirths, mummified fetus, litter weight, number of weaning live, number of weaning qualified and weaning weight. And compared the production performance of PRV gE antibody negative and positive sows in the same intensive pig farm. The study showed that each PRV gE antibody negative sow could produce 11.96 live piglets per parity. Additionally, PRV gE antibody negative sow could provide more alive, weaning and weaning qualified piglets per parity than infection sows, which were 0.63, 0.18 and 0.28, respectively. Although the average birth weight and average weaning weight of piglets produced by PRV gE antibody positive sows were higher than those produced by negative sows, the weaning qualified rate of antibody negative sows was higher than that of antibody positive sows, indicating that the weaning live piglets produced by antibody negative sows had higher uniformity. In summary, the production performance of PRV gE antibody positive sows was lower than that of the negative sows. Eradication of PR can bring higher profit to the pig farm. Pig farm should actively eradicate the PR.     

伪狂犬病病毒野毒感染猪场的gE抗体阳性头胎母猪生产成绩调查

伪狂犬病（Pseudorabies，PR）是由伪狂犬病病毒（Pseudorabies virus，PRV）感染多种野生动物及家畜引起的急性、热性的高度接触性传染病。为掌握PRV隐性感染对头胎母猪生产成绩的影响，本研究跟踪调查某一PRV野毒阳性稳定万头母猪场中野毒gE抗体阴性和阳性的头胎母猪总产仔数、健仔数、弱仔数、死胎数、木乃伊胎数、仔猪初生窝重以及断奶活仔数、断奶合格仔数、仔猪断奶重等不同生产成绩指标，探索相同饲养条件下伪狂犬病对头胎母猪各生产指标的影响。结果发现，每头PRV野毒gE抗体阴性头胎母猪每窝平均可产11.96头活仔猪，比gE抗体阳性母猪每胎次多产活仔0.63头，以及每胎次可多提供0.18头断奶活仔，每胎次多提供0.28头断奶合格仔。虽然PRV野毒gE抗体阳性母猪所产仔猪初生均重及断奶均重均高于gE抗体阴性母猪所产仔猪，但gE抗体阴性母猪所产仔猪断奶合格率高于gE抗体阳性母猪，表明其断奶活仔整齐度更高。综上，PRV野毒gE抗体阳性的头胎母猪生产成绩低于gE抗体阴性母猪，伪狂犬病的净化可为猪场带来更高的经济效益，表明伪狂犬病的净化至关重要。     

Establishment of central nervous system infection by canine distemper virus: breach of the blood-brain barrier and facilitation by antiviral antibody

Morphologic, immunologic and virologic data implicating antiviral antibody in promoting entry of canine distemper virus (CDV) into brain and reticuloendothelial tissues are reviewed. Infection of central nervous system (CNS) endothelium precedes invasion of virus-positive and -negative leukocytes into Virchow-Robin spaces and central nervous system (CNS) parenchyma by 1-3 days. Platelets are implicated in initiation of endothelial infection in that: CDV-infected dogs are thrombocytopenic; platelets from CDV-infected dogs contain IgG-virus complexes on their plasma membranes; platelet microthrombi were observed adjacent to foci of endothelial infection, and; CDV-susceptible ferrets rendered thrombocytopenic by antiplatelet antibody exhibit delayed viral entry into CNS tissues. Renal glomerular-bound IgG, IgM and occasionally CDV antigen were demonstrated in CDV-infected dogs by immunocytochemical techniques. Distemper-infected dogs with inherited C3 deficiency exhibited enhanced renal glomerular disease associated chiefly with deposition of IgM in mesengial regions vs. their homozygous normal CDV-infected littermates. Direct infusion of virus-positive leukocytes, plasma and platelets into the CNS capillary bed via the right carotid artery should establish the primacy of each in the initiation of CNS vascular endothelial infection by CDV.     

Proliferative vasculopathy and cutaneous hemorrhages in porcine neonates infected with the porcine reproductive and respiratory syndrome virus

Severe cutaneous hemorrhages with dermal and subcutaneous capillary angioplasia were seen in aborted and stillborn piglets, concurrently with an acute outbreak of porcine reproductive and respiratory syndrome virus (PRRSV) abortions. Histologically, the lesions consisted of angioblastic endothelial cells and immature capillary vascular structures coursing through the edematous myxomatous dermis and subcutis. Proliferating capillaries often were surrounded by large and foamy macrophages that stained positively for PRRSV by immunohistochemistry. The sudden appearance of these vascular lesions during the PRRSV outbreak and their abrupt disappearance after the abortion storm, along with the immunohistochemical localization of PRRSV-positive macrophages adjacent to the proliferating capillaries, suggest that PRRSV likely played a role in the development of these unusual lesions.     

Brain and spinal cord lesions in encephalitozoonosis in mink

Central nervous system lesions were studied by light microscopy in 43 farmed mink, aged 5 months to 2 1/2 years, with spontaneous encephalitozoonosis and showing cataractous eye changes. Lesions were found in the brain and spinal cord of all animals examined but were generally mild and chronic. The lesions were consistent with those previously described in spontaneous encephalitozoonosis in other carnivores. Parasites in parasitophorous vacuoles and free or phagocytosed in necrotic and granulomatous lesions were demonstrated in animals aged 5 months to 1 year. The occurrence of arterial lesions of the polyarteritis nodosa type found in the youngest animals probably indicates fetal infection. In animals aged 1 1/2 and 2 1/2 years active lesions were usually lacking and the changes were characterized by arterial sclerosis, sometimes with aneurysmal formations, small perivascular lympho-plasmacytic cuffings and focal gliosis.     

Pathogenesis of aleutian mink disease. VII. Chronic hepatitis with bile duct proliferation]

Aleutian disease is a chronic persistent viral infection of mink characterized by hypergammaglobulinema, generalized plasmacytosis, sclerosing glomerulonephritis, polyarteritis, and plasma cell hepatitis with bile duct proliferation. The development of hepatic lesions was studied both light- and electron-microscopically in mink experimentally infected with Aleutian disease virus. Fifteen normal and 99 mink experimentally infected with Aleutian disease virus were used. Experimental mink were killed in intervals from 3 weeks to 23 months after infection, and liver sections were processed for both light- and electron-microscopic studies. Experimentally infected mink developed portal and intralobular lymphocytic and plasmacytic infiltrates in the liver 3 weeks after infection. Four to five weeks after infection there was evidence of early bile duct proliferation that began as an outgrowth of the portal bile ducts. Three to five months after infection a marked bile duct proliferation was present in some of the portal triads and adjacent liver lobules; but there was no tendency of these lesions to progress into biliary cirrhosis. Ultrastructural characteristics of proliferating bile duct cells were marked deformation, formation of multiple cell layers, reduction in the number of microvilli and desmosomes, and infiltration of the epithelial cells by lymphoid cells and plasmacytes. The hepatic lesions either develop by direct virus stimulation or by the deposition of virus-antibody complexes.     

Pathology of Aujeszky's disease in mink

Lesions in 21 mink which died of Aujeszky's disease included hemorrhages in lungs, heart, mediastinum, thymus, diaphragm, gastric wall, pancreas, and enteric wall. Microscopically, hyalin and fibrinoid degeneration and necrosis of vessel walls were present in cardiac muscle, brain, gastrointestinal wall and occasionally elsewhere in the body. Hemorrhages, exudation of plasma proteins and necrosis were associated with the angiopathy. Inflammation was minimal or absent. Other findings were congestion and extravasation of blood (lungs, liver), necrosis of lymphoid cells, and hemoglobinuric nephrosis. Aujeszky's disease virus was isolated from all but three animals. After experimental infection of three mink, similar though less pronounced lesions were found to those observed in the field cases.     

Über die intramuralen Blutgefäße des Enddarms vom Pferd (Equus przewalskii f. caballus)

The vascular system of the large intestine of 12 horses was examined by means of vascular corrosion casts, histology and transmission electron microscopy providing the following results. The Aa. et Vv. breves et longae leave the mesenteric vessels, respectively the subserously on the teniae lying cecal vessels to reach the tela subserosa at the mesenteric margin. The short vessels enter the deeper layers of the wall instantly, whereas the Aa. et Vv. longae move towards the submucosa by penetrating the muscular layers after a variable subserous course. The tela submucosa contains an arterial and a venous vascular plexus. In broader areas of the submucosa a three-dimensional vascular network can be found. This consists of a deep and a superficial vascular plexus, which are closely interconnected. The deep plexus is applied to the inner circular muscles, whereas the superficial plexus is adjacent to the muscularis mucosae. The (deep) arterial plexus receives its afflux from the Aa. breves et longae and supplies parts of the circular muscle layer with recurrent muscle branches. The vascularisation of the mucosa also originates from the submucosal (superficial) plexus. In the basal tunica mucosa, the ascending arteries form a transversal network from which arterioles branch into periglandular capillaries around each Lieberkühn crypt. Close to the lumen, a polygonal subepithelial capillary system is formed. The capillaries turn into postcapillary venules immediately below the epithelium of the mucosal surface. Veins move vertically through the submucosa to enter the submucosal plexus after few inflowing side branches. Branches of the subserous-submucosal connections form an intermuscular plexus between the circular and longitudinal muscular layer. This plexus supplies the capillaries of the tunica muscularis. The subepithelial capillaries are predominantly lined with a fenestrated endothelium, whereas the capillaries of the pericryptal mucosa mainly show a continuous endothelial lining. The latter contain multiple vesicles, which may fuse in order to form transcytoplasmic channels. Sphincter-like muscle bundles at the transition points from capillaries to venules may provide hemodynamic regulatory structures in the submucosa of the horse. Veins with circumferential cushions of smooth muscle fibres, so-called ‘throttle veins’, are also found.     

A study of Bovid herpesvirus 2 infection in calves inoculated intradermally or intranasally

Bovid herpesvirus 2 infection was studied in calves exposed to the virus by intradermal inoculation of the skin of the left cheek or by nasal spray.

In either case a localised infection developed and virus replication was shown to occur mostly in the tissues of its primary localisation, i.e. the skin of the left cheek or the nasal mucosa. There were neither secondary lesions, except at the site of virus injection, nor any serious systemic involvement on the part of the animals.

The virus was also recovered from some areas of the skin (right cheek, perineum and scrotum) that were free of macroscopic lesions; moreover, intranuclear inclusions were found in several tissues of the nervous system (brain, superior cervical, stellate and Gasserian ganglia) which did not show any signs of inflammatory or degenerative changes. These findings suggest that the skin and the nervous system play an important role in the naturally-occurring disease since they could be the sites where the virus is maintained latently in the host.     

Bacterial diskospondylitis associated with posterior paresis/paralysis in North American farmed mink (Mustela vison)

Posterior paresis/paralysis in farmed mink is responsible for significant morbidity and mortality, with individual farms reporting the loss of as many as 700 animals each year. Although this disease has been recognized by North American mink farmers for approximately 40 years, there are few published reports focusing on this entity. The objective of this study was to investigate the etiology and pathogenesis of the disease. Complete necropsy examinations were done on 40 clinically affected mink, ranging from 7 to 10 weeks of age, and on three normal animals in the same age range from two mink farms. Thirty-two of the 40 clinically affected animals had an isolated vertebral lesion characterized by bone lysis and proliferation that usually was centered on an intervertebral disk space in the midthoracic area. An inflammatory reaction, composed primarily of neutrophils, was present within the vertebral sections in 25 of the 40 affected animals (62.5%), and the presence of gram-positive cocci was confirmed in 8 of 10 animals (80%) in which bacterial organisms were observed histologically. Bacterial cultures from 15 affected animals yielded Streptococcus sp. from the intervertebral disk space in 13 of 15 (86.7%) animals and from heart blood in 6 of 8 (75%). A farm visit revealed no history or evidence of traumatic wounds as a source of infection in these animals, and the diet appeared to be adequate for skeletal development. We conclude that posterior paresis/paralysis in farmed mink is associated with bacterial diskospondylitis, likely occurring secondary to bacteremia/septicemia.