Antibody response to the surface envelope of caprine arthritis-encephalitis lentivirus: disease status is predicted by SU antibody isotype

This study evaluated the hypothesis that the disease status of Saanen goats infected with caprine arthritis-encephalitis lentivirus (CAEV) is associated with the focus of immune responses to viral antigens, particularly the surface envelope glycoprotein (SU). Specifically, we have proposed that Th2 responses promote progressive immune-mediated arthritis, whereas Th1 responses restrict virus replication and development of clinical disease. The present study determined the isotype of SU antibodies associated with progressor and long-term nonprogressor (LTNP) status. We show that chronically infected goats that develop clinical arthritis have predominantly IgG1 antibodies to SU during both preclinical and clinical stages of disease, whereas SU antibodies of LTNP goats are relatively biased toward IgG2. Additional studies determined the isotype of SU antibodies induced initially by CAEV infection. These experiments show that initial IgG1-dominated responses to SU are associated with subsequent development of preclinical inflammatory joint lesions, whereas lack of joint pathology is associated with an IgG2 bias of initial responses to SU. Our results using the CAEV model suggest that isotype bias of SU antibodies is a reliable indicator of clinical disease caused by lentiviruses. Isotype analysis may be a useful method to screen candidate lentiviral vaccines intended to prevent disease progression

An insertion mutation in ABCB4 is associated with gallbladder mucocele formation in dogs

BACKGROUND: ABCB4 functions as a phosphatidylcholine translocater, flipping phosphatidylcholine across hepatocyte canalicular membranes into biliary canaliculi. In people, ABCB4 gene mutations are associated with several disease syndromes including intrahepatic cholestasis of pregnancy, progressive familial intrahepatic cholestasis (type 3), primary biliary cirrhosis, and cholelithiasis. Hepatobiliary disease, specifically gallbladder mucocele formation, has been recognized with increased frequency in dogs during the past decade. Because Shetland Sheepdogs are considered to be predisposed to gallbladder mucoceles, we initially investigated ABCB4 as a candidate gene for gallbladder mucocele formation in that breed, but included affected dogs of other breeds as well. RESULTS: An insertion (G) mutation in exon 12 of canine ABCB4 (ABCB4 1583_1584G) was found to be significantly associated with hepatobiliary disease in Shetland Sheepdogs specifically (P < 0.0001) as well as other breeds (P < 0.0006). ABCB4 1583_1584G results in a frame shift generating four stop codons that prematurely terminate ABCB4 protein synthesis within exon 12, abolishing over half of the protein including critical ATP and a putative substrate binding site. CONCLUSIONS: The finding of a significant association of ABCB4 1583_1584G with gallbladder mucoceles in dogs suggests that this phospholipid flippase may play a role in the pathophysiology of this disorder. Affected dogs may provide a useful model for identifying novel treatment strategies for ABCB4-associated hepatobiliary disease in people

Strawberry disease lesions in rainbow trout from southern Idaho are associated with DNA from a Rickettsia-like organism

Strawberry disease (SD) in the USA is a skin disorder of unknown etiology that occurs in rainbow trout Oncorhynchus mykiss and is characterized by bright red inflammatory lesions. To identify a candidate bacterial agent responsible for SD, we constructed 16S rDNA libraries from 7 SD lesion samples and 2 apparently healthy skin samples from SD-affected fish. A 16S rDNA sequence highly similar to members of the order Rickettsiales was present in 3 lesion libraries at 1%, 32% and 54% prevalence, but this sequence was not found in either healthy tissue library. Based on phylogenetic analysis, this Rickettsia-like organism (RLO) sequence is most closely related to 16S rDNA sequences of bacteria that may form a novel lineage within the Rickettsiales. We used nested PCR assays to screen 25 SD-affected fish for RLO or Flavobacterium psychrophilum DNA. Sixteen lesion samples were positive for the RLO sequence and 4 of the matched healthy samples were positive resulting in a significant association between SD lesions and presence of RLO DNA. While F. psychrophilum is reportedly associated with 'cold water strawberry disease' in the UK, we found no significant association between SD lesions and the presence of F. psychrophilum DNA. The statistical association between SD lesions and presence of RLO DNA is not proof of etiology, but these data suggest that RLO may play a role in SD in southern Idaho, USA

Integrative functional analyses using rainbow trout selected for tolerance to plant diets reveal nutrigenomic signatures for soy utilization without the concurrence of enteritis

<div><p>Finding suitable alternative protein sources for diets of carnivorous fish species remains a major concern for sustainable aquaculture. Through genetic selection, we created a strain of rainbow trout that outperforms parental lines in utilizing an all-plant protein diet and does not develop enteritis in the distal intestine, as is typical with salmonids on long-term plant protein-based feeds. By incorporating this strain into functional analyses, we set out to determine which genes are critical to plant protein utilization in the absence of gut inflammation. After a 12-week feeding trial with our selected strain and a control trout strain fed either a fishmeal-based diet or an all-plant protein diet, high-throughput RNA sequencing was completed on both liver and muscle tissues. Differential gene expression analyses, weighted correlation network analyses and further functional characterization were performed. A strain-by-diet design revealed differential expression ranging from a few dozen to over one thousand genes among the various comparisons and tissues. Major gene ontology groups identified between comparisons included those encompassing central, intermediary and foreign molecule metabolism, associated biosynthetic pathways as well as immunity. A systems approach indicated that genes involved in purine metabolism were highly perturbed. Systems analysis among the tissues tested further suggests the interplay between selection for growth, dietary utilization and protein tolerance may also have implications for nonspecific immunity. By combining data from differential gene expression and co-expression networks using selected trout, along with ontology and pathway analyses, a set of 63 candidate genes for plant diet tolerance was found. Risk loci in human inflammatory bowel diseases were also found in our datasets, indicating rainbow trout selected for plant-diet tolerance may have added utility as a potential biomedical model.</p></div

Bar chart of histopathological scoring.

<p>The Y-axis shows cumulative score, where higher scoring equals increase in severity. The X-axis indicates fish strain (HC or ARS-KO) along with treatment (PM or FM diet). The chart key and color are indicative of scoring variables: Mucosal fold fusion (MF), lamina propria width and cellularity (LP), sub-epithelial mucosa width and cellularity (SM), total inflammatory cell number (TIC), number of eosinophilic granulocytes (EG), degree of enterocyte supranuclear vacuolization (SNV) and number of goblet cells (GC).</p

Photomicrographs of distal intestines at 400x magnification.

<p>(a). A representative image of selected fish reared for 12-weeks on plant protein based feed, similar to selected and non-selected fish reared on the fishmeal based feed (b). A representative image of non-selected fish reared for 12-weeks on the plant protein based feed. Intracytoplasmic supranuclear vacuoles (asterisk), intraepithelial lymphocytes (arrowhead) and mucous cell hyperplasia (arrow) are so indicated. Scale is depicted by horizontal bar.</p

Experimental design.

<p>Experimental design.</p

Peripheral Ovine Progressive Pneumonia Provirus Levels Correlate with and Predict Histological Tissue Lesion Severity in Naturally Infected Sheep

Studies were undertaken to determine whether anti-ovine progressive pneumonia virus (OPPV) antibody responses in serum or OPP provirus levels in peripheral blood associate with the degree of histologically measured tissue lesions in naturally OPPV-infected sheep. Sections of formalin-fixed, paraffin-embedded, and hematoxylin- and eosin-stained lung, mammary gland, carpal synovial membrane, and brain tissues from 11 OPPV-infected ewes (mean age of 8.6 years) and 5 OPPV-uninfected ewes (mean age of 6 years) were evaluated for lesion severity. Ovine progressive pneumonia (OPP) provirus levels and anti-OPPV antibody titers in peripheral blood and serum samples, respectively, were measured upon euthanasia and 3 years prior to euthanasia. Both mean peripheral OPP provirus levels and mean serum anti-surface envelope glycoprotein (anti-SU) antibody titers at the time of euthanasia were significantly higher in ewes with moderate to severe histological lesions than in ewes with no to mild histological lesions. However, although mean peripheral blood OPP provirus levels at euthanasia and 3 years prior to euthanasia significantly correlated with the highest histological lesion score for any affected tissue (two-tailed P values, 0.03 and 0.02), mean serum anti-SU antibody titers, anti-capsid antibody titers, and anti-transmembrane 90 antibody titers at euthanasia did not show a significant correlation with the highest histological lesion score for any tissue (two-tailed P values, 0.32, 0.97, and 0.18, respectively). These data are the first to show that OPP provirus levels predict and correlate with the extent of OPPV-related histological lesions in various OPPV-affected tissues. These findings suggest that peripheral OPP provirus levels quantitatively contribute more to the development of histological lesions than the systemic anti-SU antibody host immune response