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Tick-borne encephalitis virus (TBEV) is a zoonotic virus in the genus Flavivirus , family Flaviviridae . TBEV is widely distributed in northern regions of the Eurasian continent, including Japan, and causes severe encephalitis in humans. Tick-borne encephalitis (TBE) was recently reported in central Hokkaido, and wild animals with anti-TBEV antibodies were detected over a wide area of Hokkaido, although TBEV was only isolated in southern Hokkaido. In this study, we conducted a survey of ticks to isolate TBEV in central Hokkaido. One strain, designated Sapporo-17-Io1, was isolated from ticks ( Ixodes ovatus ) collected in Sapporo city. Sequence analysis revealed that the isolated strain belonged to the Far Eastern subtype of TBEV and was classified in a different subcluster from Oshima 5-10, which had previously been isolated in southern Hokkaido. Sapporo-17-Io1 showed similar growth properties to those of Oshima 5-10 in cultured cells and mouse brains. The mortality rate of mice infected intracerebrally with each virus was similar, but the survival time of mice inoculated with Sapporo-17-Io1 was significantly longer than that of mice inoculated with Oshima 5-10. These results indicate that the neurovirulence of Sapporo-17-Io1 was lower than that of Oshima 5-10. Using an infectious cDNA clone, the replacement of genes encoding non-structural genes from Oshima 5-10 with those from Sapporo-17-Io1 attenuated the neuropathogenicity of the cloned viruses. This result indicated that the non-structural proteins determine the neurovirulence of these two strains. Our results provide important insights for evaluating epidemiological risk in TBE-endemic areas of Hokkaido.

Background: Norovirus is a major pathogen of gastroenteritis and is known to cause encephalitis/encephalopathy. The aim of this national survey was to clarify the clinical features of norovirus-associated encephalitis/encephalopathy (NoVE) among children in Japan., Methods: A nationwide survey of children with NoVE was conducted using a structured research form. The initial survey asked pediatricians about children with NoVE treated between January 2011 and March 2016. The second survey obtained patient information from two sources: hospitals that responded to the initial survey and those identified as having treated cases from a literature search., Results: Clinical information was available for 29 children. Their median age was 2 y 8 m. The outcome was good in 13 patients and poor in 15. The interval between the onset of gastrointestinal symptoms and that of encephalitis/encephalopathy was significantly shorter in those with a poor outcome. At the onset of an elevated serum creatinine level and an abnormal blood glucose level were correlated with a poor outcome. Regarding the subtypes of encephalitis/encephalopathy, acute encephalopathy with biphasic seizures and late reduced diffusion and hemorrhagic shock and encephalopathy syndrome were frequent., Conclusion: The outcome of children with NoVE was poor. Early onset of neurological symptoms, an elevated serum creatinine level, and an abnormal blood glucose level were associated with a poor outcome. No effective treatment was identified and this should be the subject of future studies., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis in humans. A recent epizootiological survey indicated that endemic foci of TBEV have been maintained in the southern part of Hokkaido until recently. In this study, we sought to isolate TBEV from wild rodents in the area. One virus, designated Oshima 08-As, was isolated from an Apodemus speciosus captured in Hokuto in 2008. Oshima 08-As was classified as the Far Eastern subtype of TBEV and formed a cluster with the other strains isolated in Hokkaido from 1995 to 1996. Thirty-six nucleotide differences resulted in 12 amino acid changes between Oshima 08-As and Oshima 5-10 isolated in 1995. Oshima 08-As caused high mortality and morbidity in a mouse model compared with Oshima 5-10. Although similar transient viral multiplication in the spleen was observed in the mice infected with Oshima 08-As and Oshima 5-10, greater viral multiplication with an inflammatory response was noted in the brains of mice infected with Oshima 08-As than those infected with Oshima 5-10. These data indicate that a few naturally occurring mutations affect the pathogenicity of the Oshima strains endemic in the southern part of Hokkaido.

Tick-borne encephalitis virus (TBEV) is a zoonotic agent that causes acute central nervous system (CNS) disease in humans. In this study, we examined the pathogenic process following intracerebral infection with the Oshima strain of TBEV in a mouse model. Intracerebral infection resulted in dose-dependent mortality, and all mice died following challenge with 10(2) PFU or more of the virus within 10 days. Acutely necrotic neurons and widespread inflammation were observed throughout the CNS. We therefore conclude that mortality following intracerebral infection results from a direct CNS pathology.

The pathogenicity of equine herpesvirus 1 (EHV-1) isolates of Japan were evaluated by using the CBA mouse model. CBA mice were inoculated with eight Japanese EHV-1 strains (89c1, 90c16, 90c18, 97c11, 98c12, 00c19, 01c1 and HH-1) and one British strain (Ab4p). 89c1 caused slight body weight loss and nervous signs in mice at 8 days post infection (dpi). Severe weight loss and nervous signs were observed in mice inoculated with Ab4p at 6 dpi. The other strains did not cause apparent clinical signs. Infectious viruses were recovered from the lungs of all groups at 2 dpi. Histopathological analysis revealed interstitial pneumonia in the lungs of all mice inoculated with EHV-1. Encephalitis or meningoencephalitis was observed in the brains of mice inoculated with 89c1, 90c18, 97c11, 98c12, 01c1 and Ab4p. Japanese EHV-1 strains showed low pathogenicity in CBA mice, whereas the sequential affects of infection are similar to those of the highly pathogenic strain Ab4p. These results suggest that field isolates of EHV-1 have varying degrees of pathogenicity in CBA mice.

The incidence of Epstein-Barr virus (EBV)-associated primary central nervous system (CNS) lymphoma in Japan was assessed using in situ hybridization of EBV-encoded small ribonucleic acid-1 (EBER-1) to identify the presence of EBV in 22 cases of formalin-fixed and paraffin-embedded primary CNS lymphoma. All cases were B-cell lymphoma. EBER-1 expression was observed in the nuclei of 3 of 22 primary CNS lymphoma cases (13.6%). The incidence of EBV-positive lymphoma in Japanese cases is higher than previously reported from Western countries. Patients with EBV-positive primary CNS lymphoma showed shorter survival than those with negative tumors (median 4 months vs. 26 months). EBER-1 in situ hybridization for the detection of EBV infection is rapid and reliable. Infrequent association suggests a different pathogenetic mechanism in the evolution of these tumors. Geographical differences in the incidence of EBV-associated primary CNS lymphoma may reflect epidemiological factors.

Ten wild masked palm civets infected with canine distemper virus (CDV), captured in Japan from 2005 to 2007, were histopathologically and phylogenetically analyzed. Phylogenetic analysis based on the amino acid sequences of the H protein of two CDV isolates from masked palm civets revealed that the two isolates were classified into the clade of recent isolates in Japan. Histopathologically marked lesions of virus encephalitis were present in the brain, whereas gastrointestinal lesions were absent or at a mild degree. The distribution of the lesions resembles that of recent CDV cases in dogs. Therefore, recent CDV infections in masked palm civets could be caused by recently prevalent CDV in dogs. The possibility of the masked palm civet as a spreader of CDV among wildlife is also discussed.

We have examined the seroprevalence of BDV in wild Raccoons (Procyon lotor) in Hokkaido, Japan. Serum samples from raccoons were examined using ELISA and Western blot assays to detect the presence of serum antibodies that react specifically to BDV antigens. Among 549 investigated individuals, eleven (2.0%) showed a positive reaction to BDV antigens. Brain tissue samples from five individuals were subjected to RT-PCR, which detected BDV sequences in three of them. Sequence analysis revealed a high degree of genetic conservation between BDV sequences derived from raccoons and previously published sequences derived from other animal species.

Six calves, aged between 55 days and 15 months, were presented between September and November 2006 with neurological signs including limb weakness and circling. Microscopical examination of the brain and spinal cord revealed the presence of non-suppurative encephalitis in all animals. Perivascular cuffing of lymphocytes and macrophages and diffuse gliosis was prominent in the cerebrum and degeneration and/or necrosis of neurons with vacuolation of the neuropil was present in the brainstem. Neuronal necrosis and neuronophagia were noted in the ventral horn of the spinal cord. The distribution of the lesions was closely related to the clinical signs displayed by each calf. Five calves presenting with astasia with low head carriage or torticollis had lesions throughout the central nervous system (CNS). The oldest calf displayed astasia caused by weakness of the "hindlimb" one word and had lesions largely restricted to the caudal spinal cord. Akabane virus (AKAV) antigens were detected immunohistochemically within neurons and axons in lesional tissue. Virus was not isolated from CNS tissue but the AKAV S gene was detected in this tissue from five calves by reverse transcriptase polymerase chain reaction (RT-PCR). It is suggested that AKAV infection is likely to have occurred during the early life period in the calves of this study.

Diseased wild redspotted grouper Epinephelus akaara were collected from Seto Inland Sea, Ehime Prefecture, in August 2002. Fish showed erratic swimming behavior and inflation of the swim bladder. The fish brains were positive for nodavirus in both RT-PCR and nested PCR. The sequence of the nested PCR product (177 nt) was closely related to that of a known betanodavirus, redspotted grouper nervous necrosis virus. When juvenile sevenband grouper E. septemfasciatus were challenged intravitreously with virus, abnormal swimming behavior and high mortality were observed. This is the first report on viral nervous necrosis in a wild population of redspotted grouper with clinical signs.

Background: Akabane virus is a member of the genus Orthobunyavirus in the family Bunyaviridae. It is transmitted by hematophagous arthropod vectors such as Culicoides biting midges and is widely distributed in temperate to tropical regions of the world. The virus is well known as a teratogenic pathogen which causes abortions, stillbirths, premature births and congenital abnormalities with arthrogryposis-hydranencephaly syndrome in cattle, sheep and goats. On the other hand, it is reported that the virus rarely induces encephalomyelitis in cattle by postnatal infection. A first large-scale epidemic of Akabane viral encephalomyelitis in cattle occurred in the southern part of Japan from summer to autumn in 2006. The aim of this study is to define the epidemiological, pathological and virological properties of the disease., Results: Nonsuppurative encephalomyelitis was observed in cattle that showed neurological symptoms such as astasia, ataxia, opisthotonus and hypersensitivity in beef and dairy farms by histopathological analysis. Akabane viral antigen and genome were consistently detected from the central nervous system of these animals, and the virus was isolated not only from them but also from the blood samples of clinically healthy calves in the epidemic area. The isolates were classified into genogroup I a containing the Iriki strain, which caused encephalitis of calves almost twenty years ago in Japan. Most of the affected cattle possessed the neutralizing antibody against Akabane virus. Seroconversion of the cohabitated and sentinel cattle in the epidemic area was also confirmed during an outbreak of the disease., Conclusion: The ecological and epidemiological data we have obtained so far demonstrated that the Akabane virus is not endemic in Japan. No evidence of Akabane virus circulation was observed in 2005 through nation-wide serological surveillance, suggesting that a new strain belonging to genogroup I a invaded southern Japan from overseas in the summer of 2006 and caused an unprecedented epizootic of encephalomyelitis mainly in susceptible calves. It will be necessary to reconsider the vaccine strategy to control the disease effectually.

Japanese encephalitis (JE) is a major public health problem in Southeast Asia with around 50,000 cases and 10,000 deaths per year affecting essentially children below 10 years of age. The JE virus has shown a tendency to extend to other geographic regions. JE may cause severe encephalitis and survivors are frequently left with serious neurological lesions. In the absence of an effective antiviral treatment, prevention constitutes the best defense against this disease. Besides the implementation of vector control, immunization by vaccination is available. Vector control is expensive and difficult to implement on a large scale, leaving vaccination as the best means for mass campaigns. Recent progress in the development of live attenuated vaccines has given hope of an effective vaccine, which is both easy to use and inexpensive for large scale programs.

Japanese encephalitis (JE) is a serious encephalitis caused by JE virus. Approximately 20% of JE patients die and 50% patients recover with neuro-psychiatric sequelae. In Japan, the number of JE patients was over 1000 per year in 1960s; however, the number decreased dramatically and has been less than 10 since 1990. Ministry of Health, Labour and Welfare suspended the strong recommendation for vaccination with the mouse brain-derived JE vaccine, because of cases who developed acute disseminated encephalomyelitis (ADEM) after vaccination with JE vaccine. However, it has not been fully confirmed on scientific bases that ADEM was caused by mouse brain-derived JE vaccine. Tissue culture derived-JE vaccine is under development. It is expected that this new vaccine will come to the market soon and that the recommendation of universal vaccination with JE vaccine will be implemented at the earliest occasion.

A case of acute progressive multifocal leukoencephalopathy (PML) with hyper IgM syndrome 1 is reported. Viral DNA and VP1 protein of JC virus (JCV) and BK virus (BKV) were detected by immunohistochemistry, in situ hybridization, semi-nested polymerase chain (PCR) and PCR-restriction enzyme analysis. JCV DNA and VP1 protein were found in the nuclei of oligodendrocytes. The non-coding control region (NCCR) and VP1 region of the JCV genome were sequenced; this revealed a novel rearrangement pattern of the NCCR in the brain tissue. The VP1 regions of brain and urine JCV were identical and of genotype type 2A. The BKV in the urine sample was genotype I. No BKV genome was found in the brain. The novel genomic rearrangement of the JCV NCCR in the brain tissue may have altered JCV pathogenesis to induce PML; the impaired immunity from hyper IgM syndrome 1 may have enabled the rearrangement. The JCV NCCR rearrangement in the brain may have originated from the archetypal form in the urine through deletion and duplication., (Copyright (c) 2005 Wiley-Liss, Inc.)

Betanodaviruses are the causative agents of viral nervous necrosis (VNN) or viral encephalopathy and retinopathy (VER) in cultured marine fish. A total of 131 apparently healthy fish from 30 species were collected in two geographically remote aquaculture areas, Yashima Bay (Kagawa Prefecture) and Tamanoura Bay (Nagasaki Prefecture), in Japan. The brains of fish were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR to detect the coat protein gene of betanodavirus. In Yashima Bay, two and 13 of 20 cultured fish were positive for nodavirus in RT-PCR and nested PCR, respectively, and four of five wild fish were positive only in nested PCR. In Tamanoura Bay, 28 and 99 of 106 wild fish were positive for the virus in RT-PCR and nested PCR, respectively. All the sequences of the nested PCR products (177 nt) from 27 fish species (10 cultured and 17 wild) were highly homologous to each other (99-100%) and were closely related to that of the known betanodavirus, redspotted grouper nervous necrosis virus (RGNNV). These results illustrate that large populations of cultured and wild marine fish in aquaculture areas are subclinically infected with genetically closely related betanodaviruses, suggesting an importance of such infected fish as a carrier or reservoir of betanodaviruses.

So-called fowl glioma is characterized by multiple nodular gliomatous growths associated with disseminated non-suppurative encephalitis. To investigate the possibility of the induction of the gliomatous lesions, chicks of Japanese bantams (Gallus gallus domesticus) and specific pathogen free chickens (C/O strain White Leghorn) were intracerebrally inoculated with a brain homogenate or culture supernatant from a bantam affected with fowl glioma. All bantams and 16 chickens (89%) in the inoculated groups showed non-suppurative encephalitis, and the 18 bantams (82%) and five chickens (28%) developed multiple nodules consisting of aggregations of astrocytes in the cerebrum. These astrocytes had avian leukosis virus (ALV) antigen. By Southern blot analysis, the ALV sequence was detected both in DNA prepared from the brains of the inoculated birds and in DNA from the inoculum. Ultrastructurally, tadpole-shaped particles, approximately 100 nm in diameter, were detected in the concentrated supernatant of the chicken embryo fibroblasts, and budding of the particles was noted. These results substantiated that fowl glioma of the bantams could be transmitted by intracerebral inoculation of the affected tissue and that the causal agent was an unidentified strain of ALV.

To investigate the prevalence of diseases in the Borna disease virus (BDV) antibody positive race horses, we undertook seroepidemiological studies of BDV infection on 125 culled race horses in Hokkaido, Japan. The serological study disclosed the presence of antibodies only to BDV-p40 or -p24 in 19.2% (24/125) and 3.2% (4/125) of culled horses, respectively. Antibodies to both BDV-p40 and -p24 were found in 24.0% (30/125) of these horses. Of particular note was the finding that locomotorium disorders were detectable at a significantly higher rate in BDV antibody positive horses than that in the seronegative horses. These results imply that BDV infection may possibly contribute to an increase in the incidence rate of locomotorium disorders in race horses.

A 5-month-old Japanese black bull calf and twenty-seven 1-27-day-old calves exhibiting neurological signs between August and October 1998 were examined. The bull calf exhibited rapid breathing, fever, hypersensitivity, and ataxia and was euthanized 4 days after the onset of symptoms. The 27 calves primarily exhibited ataxia, and 15 had arthrogryposis. Histological examination of the bull calf revealed perivascular infiltraction by mononuclear cells, diffuse to multifocal gliosis, and neuronal necrosis in the brain and spinal cord. Multiple malacic foci were found in the midbrain in 5 cases. In contrast, in the 15 calves necropsied in October, there were fewer inflammatory changes, but there was neuronal cell loss in the ventral horn and a decrease in myelinated axons in the lateral and ventral funiculi. Immunohistochemical examination using a rabbit antiserum against Akabane virus strain OBE-1 revealed a large amount of viral antigen in the degenerating neurons and glial cells of the bull calf, mainly in the spinal gray matter. Small amounts of viral antigen in swollen axons and a few glial cells were found in 5 of 27 calves. Thirteen of the 27 calves had high neutralization antibody titers against the Akabane virus, whereas there was no significant antibody titer in most of the calves necropsied during August. The present study revealed that viral antigen detection was very useful for the diagnosis of Akabane diseases in the 5-month-old bull calf that was suspected to be infected postnatally, while it had limited usefulness in the other young calves.

A total of 15 (T-1-T-15) domestic cats with neurological disorders in Tokyo area were examined for association with Borna disease virus (BDV). None had detectable antibodies to feline immunodeficiency virus (FIV), feline leukemia virus, feline infectious peritonitis virus and Toxoplasma gondii, and only cat T-8 had detectable antibody to FIV. Serological and molecular epidemiological studies revealed a significantly high prevalence of BDV infection in these cats: antibodies against BDV p24 and/or p40 proteins in 10/15 (66.7%) and p24 and/or p40 RNA in peripheral blood mononuclear cells in 8/15 (53.3%). Further, in situ hybridization and immunohistochemistry analyses of the autopsied brain samples derived from one of the cats (T-15) revealed BDV RNA predominantly in neuronal cells in restricted regions, such as olfactory bulb and medulla of cerebrum. Thus, BDV is present in Japanese domestic cats with neurological disorders at a high prevalence.

The present study shows that differences in pathogenicity exist among fish nodavirus strains. In challenge trials, a Japanese strain (SJ93Nag) was highly virulent to larvae of the striped jack Pseudocaranx dentex but replication was not detected in larvae of Atlantic halibut Hippoglossus hippoglossus at 6 degrees C. Conversely, a Norwegian nodavirus strain (AH95NorA) that was highly virulent to the Atlantic halibut larvae did not replicate in striped jack larvae at 20 degrees C. Occurrence of the disease viral encephalopathy and retinopathy (VER) and cumulative mortality were significantly different in the 2 species when challenged with the 2 nodavirus strains. The presence of nodavirus in nervous tissue was monitored by immunohistochemical methods. Our results support the view that the genetic diversity among nodavirus strains reflects the existence of different viral phenotypes which may be adapted to infect different host species and/or for replicating at different temperatures. Fish nodaviruses represent surveyable pathogens well suited for studying the relation between viral genotypic and phenotypic properties such as host specificity, temperature optima, neuroinvasiveness and neurovirulence.

The pathogenic characteristics of tick-borne encephalitis (TBE) virus strain (Oshima 5-10) isolated from a sentinel dog in Hokkaido, Japan, was compared by use of a mouse model with several inoculation routes to other strains of TBE virus (the Far Eastern subtype; Sofjin strain and the Western subtype; Hochosterwitz strain) and TBE complex virus (Langat virus; TP-21 strain). The degree of neuroinvasiveness of the strains in mice subcutaneously (s.c.) inoculated was Sofjin equaled Hochosterwitz which was greater than Oshima and TP-21, respectively. Neurovirulence, as determined after intracerebral inoculation was Sofjin > Oshima = Hochosterwitz > TP-21. Virus replication in the brains of mice s.c. or intracerebrally inoculated with Oshima strain was slower and of lower titer than that of Sofjin strain. Histopathological findings indicated that subarachnoid infiltration of mononuclear cells prior to necrosis of the cerebrum was characteristic in Oshima strain. These findings indicated that the Oshima strain possessed a pathogenic potential common to TBE viruses and is less virulent for mice as compared with the two other TBE strains examined.

Gazelle herpesvirus (GHV-1), correctly designated as equine herpesvirus 9, is a new type of equine herpesvirus immunologically related to equine herpesvirus 1 (EHV-1). As a sequel to a virological study, the neuropathology of encephalitis caused by GHV-1 in Thomson's gazelles (Gazella thomsoni) was examined. Seven gazelles died with or without neurological symptoms between early September and mid-October in 1993. No gross abnormalities were observed at necropsy, but all animals had non-suppurative encephalitis, characterized by necrosis and degeneration of neurons, glial reactions and perivascular cuffing in the cerebrum. Five cases showed intranuclear inclusion bodies, with the appearance of herpesvirus in the degenerating neurons. Immunohistochemically, all seven animals showed a positive reaction to EHV-1 antigen in neurons in the necrotic areas of the cortex. The clinical course and morphological features of GHV-1 encephalitis were distinct from those of EHV-1-induced encephalitis in the horse, which is characterized by vasculitis, thrombosis, ischaemia, and lack of intranuclear inclusions in neurons.

Previous seroepidemiological and molecular epidemiological studies of Borna disease virus (BDV) showed considerably high rates of infection in horses, cattle, cats, and humans in Hokkaido, Japan. Here, we further demonstrate high rates of specific antibodies to BDV and BDV RNA in peripheral blood mononuclear cells (PBMCs) from healthy sheep bred on the same island. The BDV prevalences by immunoblotting and/or reverse transcriptase PCR were 0% (0 of 19) in newborns (<1 month old), 51.7% (15 of 29) in lambs (1 to 6 months old), and 36.7% (11 of 30) in adults (>2 years old). Among animals positive for BDV, 60% of lambs and 45.5% of adults contained BDV RNA in PBMCs while 46.7% of lambs and 90.9% of adults contained specific antibodies to BDV. Thus, it is suggested that virus replication in the blood, as observed in lambs, is usually reduced in adulthood by raising immune responses to BDV.

The hemagglutination inhibition antibody titers against the JC and BK polyoma viruses (JCV and BKV, respectively) are significantly elevated in individuals exhibiting "rogue" cells among their cultured lymphocytes. However, the elevation is so much greater with respect to JCV that the BKV elevation could readily be explained by cross reactivity to the capsid protein of these two closely related viruses. The JCV exhibits high sequence homology with the simian papovavirus, simian virus 40 (SV40), and inoculation of human fetal brain cells with JCV produces polyploidy and chromosomal damage very similar to that produced by SV40. We suggest, by analogy with the effects of SV40, that these changes are due to the action of the viral large tumor antigen, a pluripotent DNA binding protein that acts in both transcription and replication. The implications of these findings for oncogenesis are briefly discussed.

The virulence of four herpes simplex virus type 2 (HSV 2) strains (K1-K4) isolated in Okinawa, Japan was investigated, and compared with four strains (C1-C4) from Chiang Mai, Thailand and a standard laboratory strain SAV. Virulence was tested on BALB/c and C57/black mice. After viral inoculation intraperitoneally, the distribution with the passage of time of the virus in the brain and other organs was also studied using the polymerase chain reaction (PCR) method and immunohistochemistry. Generally, Okinawan HSV 2 (K1, K3 and K4) were less virulent than Chiang Mai strains (C1-C4). Among the Okinawan strains, K2 was the most virulent, but slightly less so than C3 and C4. All four Chiang Mai strains (C1-C4) and one Okinawan strain (K2) were more virulent than SAV strain. The virulence of K3 was very weak and no animals died from the intraperitoneal inoculation. In the brain, viral DNA from each strain was demonstrated at 1-9 days after inoculation by the PCR method. However, K3 strain was detected in the brain only between one day and 3 days after virus inoculation, and not after day 5. Immunohistochemically, the virus antigen was first demonstrated around the 3rd ventricle at one day after viral inoculation, then strongly at the ventral hypothalamus and the temporal lobe at 3 days after viral inoculation, and slightly in the frontal lobe, hippocampus, pons and cerebellum (on day 5 after inoculation). Furthermore, in Kupffer cells in the liver and macrophages in the spleen, numerous viral antigens were demonstrated from one to 9 days after viral inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

An emerging swine disease principally involving periweaning piglets was examined. The disease was clinically characterized by lethargy, fever, emaciation, coughing, and severe abdominal breathing, hence colloquially named "Heko-heko" disease. The consistent lesions in affected piglets were diffuse interstitial pneumonia with pronounced type II pneumocytic proliferation, meningoencephalitis, and regression of the lymphoid tissues. The causal virus was isolated in primary porcine lung cell (PLC) cultures from various organs of affected piglets and showed serological relatedness to the European porcine reproductive and respiratory syndrome (PRRS) virus. Numerous virus particles, measured about 49 nm in diameter, were detected in the cytoplasm of alveolar epithelial cells and pulmonary macrophages in PLC cultures infected with the isolate. The condition could be experimentally reproduced in conventional piglets by intranasal inoculation with the isolate and the virus was reisolated from the infected animals.