Developmental environment shapes honeybee worker response to virus infection.

The consequences of early-life experiences are far reaching. In particular, the social and nutritional environments that developing animals experience can shape their adult phenotypes. In honeybees, larval nutrition determines the eventual social roles of adults as reproductive queens or sterile workers. However, little is known about the effects of developmental nutrition on important adult worker phenotypes such as disease resilience. In this study, we manipulated worker developmental nutrition in two distinct ways under semi-natural field conditions. In the first experiment, we restricted access to nutrition via social isolation by temporarily preventing alloparental care. In the second experiment, we altered the diet quality experienced by the entire colony, leading to adult bees that had developed entirely in a nutritionally restricted environment. When bees from these two experiments reached the adult stage, we challenged them with a common bee virus, Israeli acute paralysis virus (IAPV) and compared mortality, body condition, and the expression of immune genes across diet and viral inoculation treatments. Our findings show that both forms of early life nutritional stress, whether induced by lack of alloparental care or diet quality restriction, significantly reduced bees' resilience to virus infection and affected the expression of several key genes related to immune function. These results extend our understanding of how early life nutritional environment can affect phenotypes relevant to health and highlight the importance of considering how nutritional stress can be profound even when filtered through a social group. These results also provide important insights into how nutritional stress can affect honeybee health on a longer time scale and its potential to interact with other forms of stress (i.e. disease).

Pathogenesis of hemorrhagic disease caused by elephant endotheliotropic herpesvirus (EEHV) in Asian elephants (Elephas maximus).

Elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) is an acute fatal disease in elephants. Despite the fact that the underlying pathogenesis of EEHV-HD has been proposed, it remains undetermined as to what mechanisms drive these hemorrhagic and edematous lesions. In the present study, we have investigated and explained the pathogenesis of acute EEHV-HD using blood profiles of EEHV-HD and EEHV-infected cases, hematoxylin and eosin (H&E) stain, special stains, immunohistochemistry, quantitative polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR). It was found that EEHV genomes were predominantly detected in various internal organs of EEHV-HD cases. Damage to endothelial cells, vasculitis and vascular thrombosis of the small blood vessels were also predominantly observed. Increases in platelet endothelial cell adhesion molecules-1 (PECAM-1)- and von Willebrand factor (vWF)-immunolabeling positive cells were significantly noticed in injured blood vessels. The expression of pro-inflammatory cytokine mRNA was significantly up-regulated in EEHV-HD cases when compared to EEHV-negative controls. We have hypothesized that this could be attributed to the systemic inflammation and disruption of small blood vessels, followed by the disseminated intravascular coagulopathy that enhanced hemorrhagic and edematous lesions in EEHV-HD cases. Our findings have brought attention to the potential application of effective preventive and therapeutic protocols to treat EEHV infection in Asian elephants.

Identification of a Shrimp E3 Ubiquitin Ligase TRIM50-Like Involved in Restricting White Spot Syndrome Virus Proliferation by Its Mediated Autophagy and Ubiquitination.

Most tripartite motif (TRIM) family proteins are critical components of the autophagy machinery and play important roles in host defense against viral pathogens in mammals. However, the roles of TRIM proteins in autophagy and viral infection have not been studied in lower invertebrates, especially crustaceans. In this study, we first identified a TRIM50-like gene from Penaeus monodon (designated PmTRIM50-like), which, after a white spot syndrome virus (WSSV) challenge, was significantly upregulated at the mRNA and protein levels in the intestine and hemocytes. Knockdown of PmTRIM50-like led to an increase in the WSSV quantity in shrimp, while its overexpression led to a decrease compared with the controls. Autophagy can be induced by WSSV or rapamycin challenge and has been shown to play a positive role in restricting WSSV replication in P. monodon. The mRNA and protein expression levels of PmTRIM50-like significantly increased with the enhancement of rapamycin-induced autophagy. The autophagy activity induced by WSSV or rapamycin challenge could be inhibited by silencing PmTRIM50-like in shrimp. Further studies showed that rapamycin failed to induce autophagy or inhibit WSSV replication after knockdown of PmTRIM50-like. Moreover, pull-down and in vitro ubiquitination assays demonstrated that PmTRIM50-like could interact with WSSV envelope proteins and target them for ubiquitination in vitro. Collectively, this study demonstrated that PmTRIM50-like is required for autophagy and is involved in restricting the proliferation of WSSV through its ubiquitination. This is the first study to report the role of a TRIM family protein in virus infection and host autophagy in crustaceans.

Diseases of Gastropoda.

Gastropods (class Gastropoda) form the largest of the classes in the phylum Mollusca and inhabit terrestrial, fresh water and marine environments. A large number of these species are of major conservation importance and are an essential component of ecosystems. Gastropods may be deemed as pests, having a negative impact in horticulture and agriculture, whereas others may be used as a food source for human consumption and therefore are beneficial. Gastropods are susceptible to primary diseases and also act as intermediate hosts for diseases which affect other animals, including humans. The diseases described include two that are notifiable to the World Organisation for Animal Health (OIE): Xenohaliotis californiensis and Abalone viral ganglioneuritis caused by Haliotid herpesvirus-1 (HaHV-1). Research into the diseases of gastropods has often focused on those species that act as intermediate disease hosts, those that are used in research or those cultured for food. In this paper we review the viral, bacterial, fungal, parasitic and miscellaneous conditions that have been reported in gastropods and mention some of the factors that appear to predispose them to disease. The pathogenicity of a number of these conditions has not been fully ascertained and more research is needed into specifying both the etiological agent and significance in some of the diseases reported.

Challenges in Having Vaccines Available to Control Transboundary Diseases of Livestock.

The global human population is growing at a rapid rate leading to the need for continued expansion of food animal production to meet the world's increasing nutritional requirements. As a consequence of this increased production demand, the use of high volume, animal dense systems have expanded providing high quality protein at reduced costs. Backyard animal production has also expanded. This increased food animal production has facilitated the rapid spread, mutation, and adaptation of pathogens to new hosts. This scenario continues to drive the emergence and reemergence of diseases in livestock species increasing the urgency for development and availability of vaccines for transboundary animal diseases (TADs). Even though vaccines are widely recognized as being an essential tool for control of TADs, there are many scientific, economic, political, and logistical challenges to having vaccine available to control an outbreak. This article will focus on examples of the challenges associated with having vaccines available for emergency response, as well as the characteristics of 'ideal' TAD vaccines, the need for complementary diagnostic assays, and hurdles involved in bringing efficacious veterinary TAD vaccines to market including regulatory constraints and considerations for stockpiling vaccines for emergency use in non-endemic countries. Examples will also highlight the complicated interplay between animal health and human health and demonstrate the lasting benefits that can be gained from an efficacious vaccine.

Epidemiology of a SKin Ulceration Disease (SKUD) in the sea cucumber Holothuria scabra with a review on the SKUDs in Holothuroidea (Echinodermata).

Aquacultivated sea cucumbers often suffer from SKin Ulceration Diseases (SKUDs). SKUDs have been observed in six holothuroid species from nine countries. All SKUDs present a similar symptom-the skin ulceration-and can be induced by bacteria, viruses, or abiotic factors. We here provide an update on SKUDs in holothuroids and analyse the case of the SKUD observed in Holothuria scabra in Madagascar. Field observations revealed a seasonality of the disease (i.e. wintertime maximum peak). Morphological analyses of integument ulcers showed that sea cucumbers react by forming a collagen fibre plug. Metagenomic analyses revealed a higher proportion of Vibrionaceae (Gammaproteobacteria) in ulcers in comparison to the healthy integument of the same individuals. Experimental infection assays were performed with ulcer crude extracts and bacteria isolated from these extracts (e.g. Vibrio parahaemolyticus) but did not significantly induce skin ulceration. Our results suggest that the disease is not induced by a pathogen or, at the very least, that the pathogen is not found within the ulcers as the disease is not transmissible by contact. An initial cause of the SKUD in Madagascar might be the repeated and prolonged exposures to cold temperatures. Opportunistic bacteria could settle in the dermis of ulcerated individuals and promote the ulcer extension. We propose a general nomenclature for SKUDs based on the acronym of the disease, the affected sea cucumber species (e.g. Hs for Holothuria scabra), the concerned region using an ISO code 3166-2 (e.g. MG for Madagascar), the description date (e.g. 20 for the year 2020), and, when known, the inducing agent (first letter of the general taxon, b for bacteria, v for virus in currently known cases; a a if it is an abiotic inducing parameter; nothing if the inducing cause has not been precisely identified). The disease described in this work will be designated under the name SKUD Hs-MG-20.

Association between Fur Animal Necrotizing Pyoderma in breeding farm mink (Neovison vison) and reduced fertility.

BACKGROUND: The disease Fur Animal Necrotizing Pyoderma (FNP) has since 2000 been reported in many fur producing countries including Canada, Finland and Denmark. Development of FNP is characterised by rapidly forming treatment-resistant wounds on paws and in the head region. Economic losses related to FNP have been associated with mortality and decreased fur quality as well as increased veterinary costs. Also it has been suggested that FNP may be associated with reduced production results for breeding mink. The aim of this study was to evaluate if there is an association between FNP lesions in breeding animals and reduced production results based on a retrospective cohort study. RESULTS: 1465 breeding animals (244 males and 1221 females) were followed during the breeding season 2019 on five Danish mink farms. Two farms were removed from the analysis since no occurrence of FNP appeared in the observation group. After exclusion, 846 breeding animals (148 males and 698 females) remained in the analysis and were divided into two groups: exposed (EXP) or non-exposed (N-EXP) depending on the disease history of the males during mating. Females exposed to FNP positive males during breeding in average produce 14% fewer kits (P = 0.032) and these females were also more than double as likely to produce small litters (N ≥ 3) than N-EXP females. Female's from the EXP group were introduced more times to males than females in the N-EXP group (P = 0.0001, 2.5 more times in average). Females in the EXP group did not have a statistically higher risk of becoming barren (P = 0.138) though the relative risk of becoming barren was 77% higher after encountering a FNP male. CONCLUSIONS: This study shows that FNP has more economic losses for the farms than direct loss of animals. Females in contact with males with FNP lesion during breeding have a higher risk of becoming barren, and produce significantly fewer kits compared to females whom haven't been in contact with a FNP positive male.

CgMyD88s Serves as an Innate Immune System Plug During Ostreid Herpesvirus 1 Infection in the Pacific Oyster (Crassostrea gigas).

Ostreid herpesvirus-1 microvariant (OsHV-1 µVar) is considered a major infectious microbe that can reduce the survival of natural or cultured oysters in summer. Because they lack an adaptive immune system, oysters are dependent on their innate immune systems to fight pathogens. The duplication and functional divergence of innate immune genes in the oyster have been studied, but the contribution of molecular mechanisms underlying innate immunity remains to be defined. Here, we identified the interacting proteins associated with Crassostrea gigas Toll-like receptors (CgTLR) using a yeast two-hybrid (Y2H) screening system. A total of eight proteins were identified that could interact with CgTLR. Three of these appeared at least four times in the screening and were related to MyD88. Two genes encoding these MyD88-like proteins, CgMyD88-1 and CgMyD88-2, possessed typical death and TIR domains. The third gene encoding an MyD88-like protein possessed only a TIR domain, and we named it CgMyD88s. CgMyD88s interacted only with CgTLR, but not CgMyD88-1 or CgMyD88-2. Both CgMyD88-1 and CgMyD88-2 mRNAs were upregulated after OsHV-1 µVar infection, whereas the expression of CgMyD88s decreased. When overexpressed in HEK293T cells, CgMyD88-1 and CgMyD88-2 activated an NF-κB reporter, whereas CgMyD88s impaired activation induced by CgMyD88-1 or CgMyD88-2. Intriguingly, the silencing of CgMyD88s using double-stranded RNA (dsRNA)-mediated RNA interference increased the expression of CgMyD88-1 and CgMyD88-2. Taken together, our results revealed that CgMyD88-1, CgMyD88-2, and CgMyD88s may all participate in the TLR-mediated innate immune pathway and that CgMyD88s served as a plug to avoid oysters from excessive inflammatory response during OsHV-1 µVar infections.

Sea star wasting disease demography and etiology in the brooding sea star Leptasterias spp.

Sea star wasting disease (SSWD) describes a suite of disease signs believed to have led to catastrophic die-offs in many asteroid species, beginning in 2013. While most studies have focused on large, easily visible sea stars with widely-dispersing larvae, less information is available on the effect of this disease outbreak on smaller sea star species, such as the six-armed sea star Leptasterias spp. Unlike many larger sea stars, Leptasterias brood non-feeding young instead of broadcast-spawning planktonic larvae. Limited dispersal and thus limited gene flow may make these sea stars more vulnerable to local selective pressures, such as disease outbreaks. Here, we examined Leptasterias populations at sites along the California coast and documented abundance changes coincident with recent Pacific coast SSWD in 2014. Detection of Leptasterias in central California declined, and Leptasterias were not detected at multiple sites clustered around the San Francisco Bay outflow in the most recent surveys. Additionally, we categorized disease signs in Leptasterias in the field and laboratory, which mirrored those seen in larger sea stars in both settings. Finally, we found that magnesium chloride (MgCl2) slowed the progression of physical deterioration related to SSWD when applied to sea stars in the laboratory, suggesting that MgCl2 may prolong the survival of diseased individuals.

Feline Virome-A Review of Novel Enteric Viruses Detected in Cats.

Recent advances in the diagnostic and metagenomic investigations of the feline enteric environment have allowed the identification of several novel viruses that have been associated with gastroenteritis in cats. In the last few years, noroviruses, kobuviruses, and novel parvoviruses have been repetitively detected in diarrheic cats as alone or in mixed infections with other pathogens, raising a number of questions, with particular regards to their pathogenic attitude and clinical impact. In the present article, the current available literature on novel potential feline enteric viruses is reviewed, providing a meaningful update on the etiology, epidemiologic, pathogenetic, clinical, and diagnostic aspects of the infections caused by these pathogens.

Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review.

Autoimmune dermatoses targeting melanocytes have gained attention in human medicine due to their progressive nature and the social impact suffered by affected individuals. In veterinary medicine, vitiligo and the uveodermatological syndrome are the two autoimmune diseases that are known to affect skin melanocytes.In the first part of this article, we will review the signalment, clinical signs, histopathology and the treatment outcome of vitiligo in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. In a similar fashion, the information on the uveodermatological syndrome in dogs is reviewed and, where relevant, it is compared to the Vogt-Koyanagi-Harada (VKH) syndrome in humans.Canine, feline and equine vitiligo have many features that mirror their human counterparts. The most effective treatment and outcome of vitiligo in animals remain unclear. The canine uveodermatological syndrome resembles the incomplete VKH variant in humans; for affected individuals, an immediate diagnosis and aggressive treatment are crucial to prevent the development of blindness.

Increase in morbidity and mortality in a shipment of red-eared slider turtles (Trachemys scripta elegans).

A cohort of captive-bred red-eared slider turtles, Trachemys scripta, was received from a commercial vendor. Shortly after arrival, several turtles presented as lethargic with subjectively pale skin and multifocal areas of cotton-like tufts in the mouth area and distal extremities. The water was treated with a commercial anti-fungal and anti-bacterial preparation of Victoria Green B and acriflavine. Despite treatment, 10 turtles were euthanized and others demonstrated persistent clinical signs. A live turtle was submitted to a commercial diagnostic laboratory for microbiologic and histologic evaluation. Seven cultures were obtained from this turtle and numerous organisms grew from each culture, including Flavobacterium sp. Blood film analysis demonstrated intracytoplasmic gamonts of Haemogregarina sp. within erythrocytes. On necropsy, internal organs appeared to be slightly more adhered within the coelomic cavity than normal. The urinary bladder was markedly distended with turbid, dark yellow urine. Microscopic evaluation of the tissues revealed significant parasitism with Myxidium sp., Spirorchis sp. and Neopolystoma orbiculare. No fungal organisms were identified on histology or grown in culture. While there are scattered reports of these pathogens in freshwater turtles, none of the cases reported describe such extensive co-infections. It is likely that complicated infection and shipping stress exacerbated clinical signs typically seen with these organisms. Efforts to minimize stress and administration of prophylactic antiparasitic agents during the acclimation period may aid in reducing the consequences of internal parasitism in aquatic turtles.

The Expectations and Challenges of Wildlife Disease Research in the Era of Genomics: Forecasting with a Horizon Scan-like Exercise.

The outbreak and transmission of disease-causing pathogens are contributing to the unprecedented rate of biodiversity decline. Recent advances in genomics have coalesced into powerful tools to monitor, detect, and reconstruct the role of pathogens impacting wildlife populations. Wildlife researchers are thus uniquely positioned to merge ecological and evolutionary studies with genomic technologies to exploit unprecedented "Big Data" tools in disease research; however, many researchers lack the training and expertise required to use these computationally intensive methodologies. To address this disparity, the inaugural "Genomics of Disease in Wildlife" workshop assembled early to mid-career professionals with expertise across scientific disciplines (e.g., genomics, wildlife biology, veterinary sciences, and conservation management) for training in the application of genomic tools to wildlife disease research. A horizon scanning-like exercise, an activity to identify forthcoming trends and challenges, performed by the workshop participants identified and discussed 5 themes considered to be the most pressing to the application of genomics in wildlife disease research: 1) "Improving communication," 2) "Methodological and analytical advancements," 3) "Translation into practice," 4) "Integrating landscape ecology and genomics," and 5) "Emerging new questions." Wide-ranging solutions from the horizon scan were international in scope, itemized both deficiencies and strengths in wildlife genomic initiatives, promoted the use of genomic technologies to unite wildlife and human disease research, and advocated best practices for optimal use of genomic tools in wildlife disease projects. The results offer a glimpse of the potential revolution in human and wildlife disease research possible through multi-disciplinary collaborations at local, regional, and global scales.

Vaccine-associated rabies in red fox, Hungary.

Rabies vaccine strain was isolated from a red fox (Vulpes vulpes) with signs of neurological disorder during an oral vaccination campaign in 2015, Hungary. The whole genome sequence of the isolated strain shared >99.9% nucleotide sequence identity to the whole genomes of vaccines strains recently used in Hungarian oral vaccination campaigns. The neuroinvasive potential of rabies vaccines that leads to development of clinical manifestations is rarely seen among wild animals; however, the observed residual pathogenicity needs awareness of field experts and requires close monitoring of rabies cases in areas where elimination programs are implemented.

Sexual Dimorphisms in Innate Immunity and Responses to Infection in Drosophila melanogaster.

The sexes show profound differences in responses to infection and the development of autoimmunity. Dimorphisms in immune responses are ubiquitous across taxa, from arthropods to vertebrates. Drosophila melanogaster shows strong sex dimorphisms in immune system responses at baseline, upon pathogenic challenge, and over aging. We have performed an exhaustive survey of peer-reviewed literature on Drosophila immunity, and present a database of publications indicating the sex(es) analyzed in each study. While we found a growing interest in the community in adult immunity and in reporting both sexes, the main body of work in this field uses only one sex, or does not stratify by sex. We synthesize evidence for sexually dimorphic responses to bacterial, viral, and fungal infections. Dimorphisms may be mediated by distinct immune compartments, and we review work on sex differences in behavioral, epithelial, cellular, and systemic (fat body-mediated) immunity. Emerging work on sexually dimorphic aging of immune tissues, immune senescence, and inflammation are examined. We consider evolutionary drivers for sex differences in immune investment, highlight the features of Drosophila biology that make it particularly amenable to studies of immune dimorphisms, and discuss areas for future exploration.

The transcriptomic signature of low aggression in honey bees resembles a response to infection.

BACKGROUND: Behavior reflects an organism's health status. Many organisms display a generalized suite of behaviors that indicate infection or predict infection susceptibility. We apply this concept to honey bee aggression, a behavior that has been associated with positive health outcomes in previous studies. We sequenced the transcriptomes of the brain, fat body, and midgut of adult sibling worker bees who developed as pre-adults in relatively high versus low aggression colonies. Previous studies showed that this pre-adult experience impacts both aggressive behavior and resilience to pesticides. We performed enrichment analyses on differentially expressed genes to determine whether variation in aggression resembles the molecular response to infection. We further assessed whether the transcriptomic signature of aggression in the brain is similar to the neuromolecular response to acute predator threat, exposure to a high-aggression environment as an adult, or adult behavioral maturation. RESULTS: Across all three tissues assessed, genes that are differentially expressed as a function of aggression significantly overlap with genes whose expression is modulated by a variety of pathogens and parasitic feeding. In the fat body, and to some degree the midgut, our data specifically support the hypothesis that low aggression resembles a diseased or parasitized state. However, we find little evidence of active infection in individuals from the low aggression group. We also find little evidence that the brain molecular signature of aggression is enriched for genes modulated by social cues that induce aggression in adults. However, we do find evidence that genes associated with adult behavioral maturation are enriched in our brain samples. CONCLUSIONS: Results support the hypothesis that low aggression resembles a molecular state of infection. This pattern is most robust in the peripheral fat body, an immune responsive tissue in the honey bee. We find no evidence of acute infection in bees from the low aggression group, suggesting the physiological state characterizing low aggression may instead predispose bees to negative health outcomes when they are exposed to additional stressors. The similarity of molecular signatures associated with the seemingly disparate traits of aggression and disease suggests that these characteristics may, in fact, be intimately tied.

Investigative Diagnostic Toxicology and the Role of the Veterinarian in Pet Food-Related Outbreaks: An Update.

Although most commercial pet foods are safe, there have been a few instances in which chemical or bacterial contamination have caused outbreaks of illness in animals. Because of concerns regarding cases of contaminated commercial pet food that have been reported over the past several years, some pet owners may be choosing to feed noncommercial, home-prepared diets. When pet food contamination is suspected, pet owners often seek advice from their veterinarian regarding its health impact and subsequent diagnosis. This article addresses the role of the veterinarians in pet food contamination and highlights recommended approaches to handling pet food outbreaks or recalls.