Are anti-ganglioside antibodies associated with proventricular dilatation disease in birds?

The identification of Parrot bornaviruses (PaBV) in psittacine birds with proventricular dilatation disease (PDD) has not been sufficient to explain the pathogenesis of this fatal disease, since not all infected birds develop clinical signs. Although the most accepted theory indicates that PaBV directly triggers an inflammatory response in this disease, another hypothesis suggests the disease is triggered by autoantibodies targeting neuronal gangliosides, and PDD might therefore resemble Guillain-Barré Syndrome (GBS) in its pathogenesis. Experimental inoculation of pure gangliosides and brain-derived ganglioside extracts were used in two different immunization studies. The first study was performed on 17 healthy chickens (Gallus gallus domesticus): 11 chickens were inoculated with a brain ganglioside extract in Freund’s complete adjuvant (FCA) and six chickens inoculated with phosphate-buffered saline. A second study was performed five healthy quaker parrots (Myiopsitta monachus) that were divided into three groups: Two quaker parrots received purified gangliosides in FCA, two received a crude brain extract in FCA, and one control quaker parrot received FCA alone. One chicken developed difficult in walking. Histologically, only a mild perivascular and perineural lymphocytic infiltrate in the proventriculus. Two quaker parrots (one from each treatment group) had mild lymphoplasmacytic encephalitis and myelitis. However, none of the quaker parrots developed myenteric ganglioneuritis, suggesting that autoantibodies against gangliosides in birds are not associated with a condition resembling PDD

Pathological Aspects and Pathogenesis of Parrot Bornavirus 2 (PaBV-2) Infection in Psittacine Birds

Parrot bornaviruses (PaBVs) are RNA viruses of the Bornaviridae family and the causative agents of proventricular dilatation disease (PDD). PDD has many aspects that remain to be elucidated, including the mechanisms involved in its pathogenesis. The purpose of this work was to investigate different hypotheses linked to the pathogenesis of Parrot bornavirus 2 (PaBV-2) infection in psittacine birds. We first tested the hypothesis of antibodies against gangliosides being involved in the development of PDD in psittacine birds. We analyzed the relationship between the presence of antiganglioside antibodies and microscopic lesions related to PDD in birds. No association between the presence of anti-ganglioside antibodies and the development of lesions resembling PDD was observed in our study, which corroborates with the hypothesis that PDD is not an auto-immune disease as previously speculated. Second, we analyzed the progression of viral antigen and inflammatory lesions after the intramuscular inoculation of PaBV-2 in cockatiels. Histopathological, immunohistochemical and molecular analyses were performed in tissues of cockatiels in a chronological fashion. PaBV-2 was first detected in leukocytes in the inoculation site and adjacent nerves, then reached the brachial plexus, centripetally spread to the thoracic segment of the spinal cord, and subsequently invaded the other spinal segments and brain. PaBV-2 then centrifugally spread out of the central nervous system (CNS) to peripheral ganglia. Our results demonstrate that PaBV-2 first targets the CNS, before migrating to peripheral tissues such as the GI system. Finally, we aimed to evaluate the distribution of inflammatory foci and viral antigen throughout 4 selected levels of brain and 3 segments of spinal cord in cockatiels experimentally infected with PaBV-2. Immunolabeling was first observed in the ventral horns of the thoracic spinal cord. Inflammatory lesions were first identified in the gray matter of the thalamus and brainstem. Encephalitis was more severe in the thalamus and brainstem, while myelitis was equally distributed between all segments of the spinal cord. Our results demonstrate a caudal-rostral viral distribution of PABV-2. Our results reemphasize the role of PaBVs as the causative agents of PDD; the lack of an autoimmune component; and the detection of PaBV-2 in the CNS before peripheral organs

Proventricular dilatation disease (PDD) outbreak in blue-and-gold macaws (Ara ararauna) in the State of Santa Catarina, southern Brazil

ABSTRACT: Proventricular dilatation disease (PDD) is a lethal and important disease of captive psittacine birds, and affects a wide range of species, including endangered ones, and lacks an effective treatment. This report describes PDD in three blue-and-gold macaws (Ara ararauna) in southern Brazil. All three macaws originated from the same aviary and presented similar clinical signs including anorexia, apathy, emaciation and prostration. At necropsy, one of the macaws presented an enlarged proventriculus. Histologically, lymphoplasmacytic infiltrates was observed in the ganglia and nerves of the esophagus, crop, proventriculus, ventriculus, heart, adrenal glands, and adrenal medulla of all three cases. Two macaws had meningoencephalomyelitis and one had myocarditis. Immunohistochemistry identified PaBV antigen in the brain, proventricular, ventricular ganglia, and epicardial ganglia, and cardiomyocytes of all three macaws

From nerves to brain to gastrointestinal tract: A time-based study of parrot bornavirus 2 (PaBV-2) pathogenesis in cockatiels (<i>Nymphicus hollandicus</i>)

<div><p>Parrot bornaviruses (PaBVs) are the causative agents of proventricular dilatation disease, however key aspects of its pathogenesis, such as route of infection, viral spread and distribution, and target cells remain unclear. Our study aimed to track the viral spread and lesion development at 5, 10, 20, 25, 35, 40, 60, 80, 95 and 114 dpi using histopathology, immunohistochemistry, and RT-PCR. After intramuscular inoculation of parrot bornavirus 2 (PaBV-2) in the pectoral muscle of cockatiels, this virus was first detected in macrophages and lymphocytes in the inoculation site and adjacent nerves, then reached the brachial plexus, centripetally spread to the thoracic segment of the spinal cord, and subsequently invaded the other spinal segments and brain. After reaching the central nervous system (CNS), PaBV-2 centrifugally spread out the CNS to the ganglia in the gastrointestinal (GI) system, adrenal gland, heart, and kidneys. At late points of infection, PaBV-2 was not only detected in nerves and ganglia but widespread in the smooth muscle and/or scattered epithelial cells of tissues such as crop, intestines, proventriculus, kidneys, skin, and vessels. Despite the hallmark lesion of PaBVs infection being the dilation of the proventriculus, our results demonstrate PaBV-2 first targets the CNS, before migrating to peripheral tissues such as the GI system.</p></div

Summary of inflammatory lesions, PCR and IHC results observed in 12 sequential timepoints following days post infection.

<p>Summary of inflammatory lesions, PCR and IHC results observed in 12 sequential timepoints following days post infection.</p

Gross findings.

<p>Comparison of proventriculus size (arrowheads) in a control (A) and infected (B) cockatiels of the same timepoint (35 dpi). Note the distention of the proventricular wall in CK19 when compared to a control cockatiel (CK15).</p

Distribution of infected (green) and control (blue) cockatiels throughout timepoints.

<p>Cockatiels that naturally died during the experiment are represented in orange.</p

Role of metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) in pancreatic cancer - Fig 5

<p><b>(A) The structure of CDDO-Me and CF</b>_<b>3</b><b>DODA-Me.</b> Panc1 cells were treated with different concentrations of CDDO-Me or in combination of GSH, CF₃DODA-Me or in combination with GSH, and the changes of different proteins (B) and MALAT-1 expression (C) were determined by western blot and real time PCR, respectively. (D) Panc1 cells were transfected with siSp1/3/4 or siCtrl, and the MALAT-1 RNA expression was determined by real time PCR. Significant (p<0.05) changes are indicated (*) or (**).</p

Role of metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) in pancreatic cancer - Fig 6

<p><b>(A) Fold-change in MALAT-1 gene expression in knockout mice as compared to the wild type.</b> (B) Sp1, Sp3, Sp4 and c-Myc expression in homozygous floxed p53/Kras^GD12 mice. (C) Survival of homozygous floxed p53L/L: Kras^GD12:p48Cre+/- mice expression MALAT-1 (+) or with loss of MALAT-1 (-/+). (D) Survival of heterozygous floxed p53L/+: Kras^GD12:p48Cre+/- mice expression MALAT-1 (+) or with loss of MALAT-1 (-/+). (E) Histology analysis of tumor samples from different strains of mice; images were 200X and 600X (for corner inserts). p-Values for significant differences in (C) and (D) were 0.39 and 0.26, respectively.</p

Effects of MALAT-1 in pancreatic cell proliferation, cell cycle, apoptosis, migration and invasion.

<p>(A) MALAT-1 knockdown by RNAi in Panc1, MiaPaCa2 inhibited cell growth. (B) The effect of siMALAT-1 (knockdown) on cell cycle progression in Panc1 and MiaPaCa2 cells was determined by FACS analysis. (C) The apoptotic cells were quantified using FACS analysis and induction of PARP cleavage was determined by western blot analysis. MALAT-1 knockdown reduced cell migration (D) and cell invasion (E) as determined by scratch assay and Boyden chamber assay, respectively. Significant (p<0.05) changes are indicated (*).</p