The tissue distribution and cellular localization of viral antigens in three cattle with persistent bovine viral diarrhea virus (BVDV) infection was studied. In three cases, necropsy findings of oral ulcers, abmasal ulcers and necrosis of Peyer's patches were suspected have been caused by BVDV infection. Non-cytopathic BVDV was isolated from a tissue pool of liver, kidneys and spleen. Immunohistochemical detection of BVDV showed that BVDV antigens were detected in both epithelial and nonepithelial cells in all examined organs, including the gastrointestinal tract, liver, pancreas, lung, lymphatic organs (spleen, lymph nodes), adrenal gland, ovary, uterus, and the mammary gland. These findings support the hypothesis that animals with persistent BVDV infection spread BVDV through all routes, and that infertility in BVDV infection is associated with the infection of BVDV in the ovaries and uteri.
Adrenal Glands/pathology/virology ; Animals ; Antigens, Viral/*isolation & purification ; Bovine Virus Diarrhea-Mucosal Disease/pathology/physiopathology/*virology ; Cattle ; Diarrhea Viruses, Bovine Viral/immunology/*isolation & purification ; Digestive System/pathology/virology ; Female ; Immunohistochemistry/veterinary ; Infertility, Female/virology ; Kidney/pathology/virology ; Lung/pathology/virology ; Lymphatic System/pathology/virology ; Mammary Glands, Animal/virology ; Ovary/pathology/virology ; Uterus/pathology/virology

OBJECTIVETo investigate the ultrastructural changes of the extraintestinal organs of newborn mice with human retrovirus (RV) infection to probe into the mechanism and clinical diagnose and therapy of extraintestinal RV infection.

METHODSHuman RV was inoculated into the abdominal cavity of the newborn mice, and the ultrastructural changes of the heart, lung, livers, and kidneys of the infected and control mice were observed by transmission electron microscope.

RESULTSThe mice with intraabdominal RV injection showed pathological changes of the cells in the small intestinal villus, liver, and kidneys. Shortened small intestinal villus, nuclear membrane disorganization, massive vacuolization, mitochondrial swelling and rough endoplasmic reticulum dilation were observed in the cells of the small intestinal. In the liver of the mice, marked mitochondrial swelling and agglutination, cell nucleus pyknosis or collapse, presence of numerous lipid droplets and vacuoles were seen in the liver cells, with lymphocyte and plasmacyte infiltration. Obvious dilatation and shedding of the microvillus were seen in cholangioles. The mitochondria of the proximal convoluted renal tubule showed mild swelling, but the cells in the heart and lung did not display obvious changes.

CONCLUSIONThe small intestinal villi were highly susceptible to RV infection, and systemic spread of human RV may cause damage of various extraintestinal organs especially the liver, which can also be susceptible to RV.

Animals ; Animals, Newborn ; Female ; Intestine, Small ; ultrastructure ; virology ; Kidney ; ultrastructure ; virology ; Liver ; ultrastructure ; virology ; Lung ; ultrastructure ; virology ; Male ; Mice ; Microscopy, Electron, Transmission ; Rotavirus Infections ; pathology ; virology

C57BL/6 mice were inoculated intranasally (50 microl) with serial 10-fold dilution of HAB/01 H5N1 virus. Three and five days later, three mice of each group were euthanized. Lung injury was assessed by observation of lung histopathology, virus titers and MCD50 were also measured. Our data showed that H5N1 viral infection in mice resulted in mainly epithelial injury and interstitial pneumonia, featuring significant weight loss, dramatically increased lung wet weight:body weight ratio, inflammatory cellular infiltration, alveolar and interstitial edema, hemorrhage in lungs with high virus titers, and MCD50 was 10(-6.5)/ 0.05 mL. These results suggested that a mouse model of H5N1 viral infection was successfully established which may benefit study of H5N1 avian influenza virus and pathogenic mechanism of host.
Animals ; Brain ; pathology ; virology ; Disease Models, Animal ; Female ; Humans ; Influenza A Virus, H5N1 Subtype ; pathogenicity ; Influenza, Human ; pathology ; virology ; Liver ; pathology ; virology ; Lung ; pathology ; virology ; Mice ; Mice, Inbred C57BL ; Random Allocation ; Spleen ; pathology ; virology

In order to investigate the human cytomegalovirus (HCMV) infection, the mouse cytomegalovirus (MCMV) infected mice were experimentally studied. 6 to 8 week old female BALB/C mice with immunosuppression were selected to undergo the MCMV inoculations: intracranial inoculation and peritoneal inoculation. MCMV of the infected mice in various organs and tissues were detected by using beta-gal staining and in situ nucleic acid hybridization assay. The pathological changes were observed in HE staining paraffin-embedded sections. It was found that all the MCMV infected mice showed the retardation of growth and development, and feather looseness. Both intracranial inoculation of 10(4) PFU viruses or peritoneal inoculation of 10(6) PFU viruses resulted in the pathological changes, to some extent, of various organs and tissues in the mice. The pathological changes in liver were consistent with the amount of beta-gal staining positive cells, indicating the liver lesions were mainly caused by viral proliferation. It was also found that the viruses in the immunosuppressed mice subjected to intracranial inoculation could spread to whole body organs, while the viruses in the immunosuppressed mice subjected to intrapeitoneal inoculation couldn't spread to the brain, suggesting blood-brain barrier could prevent the virus from spreading to the brain.
Blood-Brain Barrier ; Brain/pathology ; Brain/virology ; Disease Models, Animal ; *Herpesviridae Infections/pathology ; *Herpesviridae Infections/virology ; Immunocompromised Host ; Liver/pathology ; Liver/virology ; Lung/pathology ; Lung/virology ; Mice, Inbred BALB C ; *Muromegalovirus

OBJECTIVETo document ultrastructural changes of brain, spinal cord, skeletal muscle, jejunum and lung of EV71 infection mouse model, and to explore the myotropism and pathogenesis of EV71 in nervous system.

METHODSTen-day-old suckling mice were infected with EV71 strain via the intraperitoneal route. Mice with paralysis were scarified on day 4 post infection and the brain, spinal cord, skeletal muscle, jejunum and lung were sampled for transmission electron microscopy and light microscopy.

RESULTSLesions in brain were generally mild with inner chamber swelling in some of mitochondria. Myelin sheaths of medullated fibers were split with vacuolated changes. The Nissl bodies in anterior motor neurons disappeared along with mitochondria swelling, rough endoplasmic reticulum swelling and degranulation. Cytoplasm of anterior motor neurons showed cribriform appearance accompanied by neuronophagia. The bands of skeletal muscle in the infected group disappeared with degeneration and karyopyknosis in myocytes, in addition to mitochondrial swelling. Microvilli of epithelium in jejunum became loosely arranged along with formation of spiral medullary sheath structure and mitochondria swelling. Interstitial pneumonia was observed in lungs with type II pneumocyte proliferation and evacuation of the multilamellar bodies.

CONCLUSIONSEV71 infection causes severe myositis in the mouse model suggesting a strong myotropism of EV71 virus. The presence of lesions of various degrees in central nervous system and changes in anterior motor neurons may be associated with limb paralysis.

Animals ; Brain ; ultrastructure ; virology ; Disease Models, Animal ; Enterovirus A, Human ; Enterovirus Infections ; pathology ; virology ; Jejunum ; ultrastructure ; virology ; Lung ; ultrastructure ; virology ; Mice ; Mice, Inbred BALB C ; Microscopy, Electron, Transmission ; Muscle, Skeletal ; ultrastructure ; virology ; Spinal Cord ; ultrastructure ; virology

In order to investigate the human cytomegalovirus (HCMV) infection, the mouse cytomegalovirus (MCMV) infected mice were experimentally studied. 6 to 8 week old female BALB/C mice with immunosuppression were selected to undergo the MCMV inoculations: intracranial inoculation and peritoneal inoculation. MCMV of the infected mice in various organs and tissues were detected by using beta-gal staining and in situ nucleic acid hybridization assay. The pathological changes were observed in HE staining paraffin-embedded sections. It was found that all the MCMV infected mice showed the retardation of growth and development, and feather looseness. Both intracranial inoculation of 10(4) PFU viruses or peritoneal inoculation of 10(6) PFU viruses resulted in the pathological changes, to some extent, of various organs and tissues in the mice. The pathological changes in liver were consistent with the amount of beta-gal staining positive cells, indicating the liver lesions were mainly caused by viral proliferation. It was also found that the viruses in the immunosuppressed mice subjected to intracranial inoculation could spread to whole body organs, while the viruses in the immunosuppressed mice subjected to intrapeitoneal inoculation couldn't spread to the brain, suggesting blood-brain barrier could prevent the virus from spreading to the brain.
Animals ; Blood-Brain Barrier ; Brain ; pathology ; virology ; Disease Models, Animal ; Female ; Herpesviridae Infections ; pathology ; virology ; Immunocompromised Host ; Liver ; pathology ; virology ; Lung ; pathology ; virology ; Mice ; Mice, Inbred BALB C ; Muromegalovirus

BACKGROUNDTo explore the pathological features and pathogenesis of severe acute respiratory syndrome (SARS) to provide evidence for the clinical treatment and prevention of SARS.

METHODSPathological features of 2 cases of full autopsy and 4 cases of needle biopsy tissue samples from the patients who died from SARS were studied by light and electron microscopy. The distribution and quantity of lymphocyte subpopulations in the lungs and immune organs from SARS patients were analyzed by immunohistochemistry. The location and semi-quantitative analysis of SARS coronavirus in the tissue specimens were studied by electron microscopy, in situ hybridization and immunohistochemistry.

RESULTSIn total of 6 cases, diffuse alveolar damage and alveolar cell proliferation were common. The major pathological changes of 2 autopsy cases of SARS in lung tissues were acute pulmonary interstitial and alveolar exudative inflammation, and 2 autopsy and one biopsy lung tissues showed alveolar hyaline membrane formation. Terminal bronchiolar and alveolar desquamation of lung tissues in one autopsy and 2 biopsy cases were noted. Among 6 cases, 2 biopsy cases presented early pulmonary fibrosis and alveolar organization. Meanwhile, the immune organs, including lymph nodes and spleens from 2 autopsy cases of SARS whose disease courses were less than 12 days showed extensive hemorrhagic necrosis, reactive macrophage/histocyte proliferation, with relative depression of mononuclear and granulocytic clones in the bone marrows. However, spleen and bone marrow biopsy tissue samples from 4 dead SARS cases whose clinical course lasted from 21 to 40 days presented repairing changes. SARS coronaviruses were mainly identified in type I and II alveolar epithelia, macrophages, and endothelia; meanwhile, some renal tubular epithelial cells, cardiomyocytes, mucosal and crypt epithelial cells of gastrointestinal tracts, parenchymal cells in adrenal glands, lymphocytes, testicular epithelial cells and Leydig's cells were also detected by electron microscopy combined with in situ hybridization. The semi-quantitative analysis of lymphocyte subpopulations revealed that the proportion of CD8+ T lymphocytes were about 80% of the total infiltrative inflammatory cells in the pulmonary interstitium, with a few CD4+ lymphocytes CD3+, CD4+, CD8+ or CD20+ lymphocyte subpopulations were obviously decreased and there was imbalance in number and proportion, while CD57+, CD68+, S-100+ and HLA-DR+ cells were relatively increased in lymph nodes and spleens.

CONCLUSIONSHistologically, the pulmonary changes could be divided into acute inflammatory exudative, terminal bronchiolar and alveolar desquamative and proliferative repair stages or types during the pathological process of SARS. SARS coronavirus was found in multi-target cells in vivo, which means that SARS coronavirus might cause multi-organ damages which were predominant in lungs. There were varying degrees of decrease and imbalance in number and proportion of lymphocyte subpopulations in the immune organs of the patients with SARS. However, these changes may be reversible. It was found that cellular immune responses were predominant in the lungs of SARS cases, which might play an important role in getting rid of coronaviruses in infected cells and inducing immune mediated injury.

Aged ; Female ; Humans ; Lung ; immunology ; pathology ; virology ; Lymphocyte Subsets ; immunology ; Male ; Middle Aged ; SARS Virus ; isolation & purification ; ultrastructure ; Severe Acute Respiratory Syndrome ; immunology ; pathology ; virology

Objective: To analyse the clinical history, laboratory tests and pathological data of a patient who suffered from novel coronavirus pneumonia(COVID-19) and provide reference for the clinical treatment of similar cases. Methods: Data of clinical manifestation, laboratory examination, bronchoscopy, echocardiography and cardiopulmonary pathological results were retrospectively reviewed in a case of COVID-19 with rapid exacerbation from mild to critical condition. Results: This patient hospitalized at day 9 post 2019 novel coronavirus(2019-nCoV) infection, experienced progressive deterioration from mild to severe at day 12, severe to critical at day 18 and underwent extracorporeal membrane oxygenation(ECMO) and continuous renal replacement therapy(CRRT) as well as heart lung transplantation during day 28-45 post infection, and died at the second day post heart and lung transplantation. The patient had suffered from hypertension for 8 years. At the early stage of the disease, his symptoms were mild and the inflammatory indices increased and the lymphocyte count decreased continuously. The patient's condition exacerbated rapidly with multi-organ infections, and eventually developed pulmonary hemorrhage and consolidation, pulmonary hypertension, right heart failure, malignant ventricular arrhythmias, liver dysfunction, etc. His clinical manifestations could not be improved despite viral RNAs test results became negative. The patient underwent lung and heart transplantation and finally died of multi organ failure at the second day post lung and heart transplantation. Pathological examination indicated massive mucus, dark red secretions and blood clots in bronchus. The pathological changes were mainly diffused pulmonary hemorrhagic injuries and necrosis, fibrosis, small vessel disease with cardiac edema and lymphocyte infiltration. Conclusions: The clinical course of severe COVID-19 can exacerbate rapidly from mild to critical with lung, liver and heart injuries.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/pathology* ; Fatal Outcome ; Hemorrhage/virology* ; Humans ; Lung/pathology* ; Myocardium/pathology* ; Pandemics ; Pneumonia, Viral/pathology* ; Retrospective Studies ; SARS-CoV-2

To explore the infectivity characteristics and susceptibility of Sendai strain Tianjin in 129Sv, DBA/2, Kunming and BALB/c mice and determine the optimal small rodent animal model for strain Tianjin research, the Sendai strain Tianjin was propagated for 72h in 9-11 day-old chicken embryos, the allantoic fluids were then harvested and the virus titer (1:1280) was detected by hemagglutination assay. Four different kinds of mice were intranasally inoculated with 5 microl and the diluted 30 microl virus solution. The weight loss of mice was monitored for 12 consecutive days and the survival rate was observed. Kunming and BALB/c mice were sacrificed on the first day prior to infection and on the fourth and seventh days post infection of the diluted 30 microl Sendai strain Tianjin. Their left lobes of lung were fixed with 4% formalin for histopathologic examination. The maximum percentage of average weight loss of 129Sv, DBA/2 were 13.0%, 4.7% with 100% survival rate when 129Sv, DBA/2, Kunming and BALB/c were inoculated with 5 microl virus solution, while the mice were inoculated with diluted 30 microl virus solution, the maximum percentage of average weight loss reached 21.7%, 30.3%, 16.7% and 9.7% with the survival rate of 20%, 0%, 80% and 100%. Lung infections of mice Kunming on the fourth and seventh day post infection were more severe than that of BALB/c, showing a large number of inflammatory cell exudation and thickening of the submucosa. It suggested that DBA/2 was the most susceptible to the infection of strain Tianjin. The mice susceptibility ranked as DBA/2>129Sv>Kunming>BALB/c. Mice DBA/2 and 129Sv could be used as the optimal small rodent animal models in the research of pathogenicity and vaccine of Sendai strain Tianjin.
Animals ; Disease Susceptibility ; Female ; Humans ; Lung ; pathology ; virology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred DBA ; Respirovirus Infections ; physiopathology ; virology ; Sendai virus ; classification ; physiology

OBJECTIVESTo examine the Epstein-Barr virus (EBV) in primary lung carcinoma tissue, and to investigate the relationship between EBV infection and tumorigenesis of lung cancer.

METHODSFormalin-fixed and paraffin-embedded lung tissue specimens from surgically resected lung carcinoma tissues of 108 cases treated in Tanshan area from 2001 to 2006, which were confirmed further by histopathological examination after hematoxylin-eosin (HE) staining, were used to observe the EBV encoded RNA-1 (EBER1) using in situ hybridization (ISH).

RESULTSEBER1 was detected in 36 of the 108 primary lung carcinoma cases, and in 1 of the 22 normal lung tissues. The positive rates of EBV infection in squamous cell carcinoma, adenocarcinoma, small cell carcinoma and large cell carcinoma were 35.9%, 31.6% 31.0%, 1/2, respectively. Gender, age and clinicohistopathological type were not found to have any correlation with EBER1 expression, but EBER1 expression in groups of cases with poorly and moderately differentiated carcinomas was significantly higher than those in the group of cases with well differentiated carcinoma, and the EBER1 expression in the right lung was higher than in the left lung.

CONCLUSIONSThe frequency of EBV infection in this series of patients from Tangshan area was 33.3%, the results suggest that there is a relationship between EBV infection and the occurrence of the primary lung carcinoma, EBV infection might be one of the potential causes to induce lung cancer.

Epstein-Barr Virus Infections ; diagnosis ; virology ; Herpesvirus 4, Human ; genetics ; Humans ; In Situ Hybridization ; methods ; Lung Neoplasms ; pathology ; virology ; RNA, Viral ; genetics