Adrenal Gland and Lung Lesions in Gulf of Mexico Common Bottlenose Dolphins (Tursiops truncatus) Found Dead following the Deepwater Horizon Oil Spill.

A northern Gulf of Mexico (GoM) cetacean unusual mortality event (UME) involving primarily bottlenose dolphins (Tursiops truncatus) in Louisiana, Mississippi, and Alabama began in February 2010 and continued into 2014. Overlapping in time and space with this UME was the Deepwater Horizon (DWH) oil spill, which was proposed as a contributing cause of adrenal disease, lung disease, and poor health in live dolphins examined during 2011 in Barataria Bay, Louisiana. To assess potential contributing factors and causes of deaths for stranded UME dolphins from June 2010 through December 2012, lung and adrenal gland tissues were histologically evaluated from 46 fresh dead non-perinatal carcasses that stranded in Louisiana (including 22 from Barataria Bay), Mississippi, and Alabama. UME dolphins were tested for evidence of biotoxicosis, morbillivirus infection, and brucellosis. Results were compared to up to 106 fresh dead stranded dolphins from outside the UME area or prior to the DWH spill. UME dolphins were more likely to have primary bacterial pneumonia (22% compared to 2% in non-UME dolphins, P = .003) and thin adrenal cortices (33% compared to 7% in non-UME dolphins, P = .003). In 70% of UME dolphins with primary bacterial pneumonia, the condition either caused or contributed significantly to death. Brucellosis and morbillivirus infections were detected in 7% and 11% of UME dolphins, respectively, and biotoxin levels were low or below the detection limit, indicating that these were not primary causes of the current UME. The rare, life-threatening, and chronic adrenal gland and lung diseases identified in stranded UME dolphins are consistent with exposure to petroleum compounds as seen in other mammals. Exposure of dolphins to elevated petroleum compounds present in coastal GoM waters during and after the DWH oil spill is proposed as a cause of adrenal and lung disease and as a contributor to increased dolphin deaths.

Morbillivirus infections: an introduction.

Research on morbillivirus infections has led to exciting developments in recent years. Global measles vaccination coverage has increased, resulting in a significant reduction in measles mortality. In 2011 rinderpest virus was declared globally eradicated - only the second virus to be eradicated by targeted vaccination. Identification of new cellular receptors and implementation of recombinant viruses expressing fluorescent proteins in a range of model systems have provided fundamental new insights into the pathogenesis of morbilliviruses, and their interactions with the host immune system. Nevertheless, both new and well-studied morbilliviruses are associated with significant disease in wildlife and domestic animals. This illustrates the need for robust surveillance and a strategic focus on barriers that restrict cross-species transmission. Recent and ongoing measles outbreaks also demonstrate that maintenance of high vaccination coverage for these highly infectious agents is critical. This introduction briefly summarizes the most important current research topics in this field.

Receptor (SLAM [CD150]) recognition and the V protein sustain swift lymphocyte-based invasion of mucosal tissue and lymphatic organs by a morbillivirus.

Experimental infections of ferrets with canine distemper virus (CDV) recapitulate many hallmarks of measles: rash, high fever, viremia, depression of delayed-type hypersensitivity responses, lowered leukocyte counts, and reduced lymphocyte proliferation activity. To understand how a morbillivirus invades the host and causes immunosuppression, we generated CDV either unable to recognize one of the receptors or incapable of expressing either one or both of the candidate interferon antagonist proteins V and C. Variants of these viruses expressing green fluorescent protein were also generated. Striking similarities between CDV infection of ferrets and human immunodeficiency virus host invasion were documented: first, massive early replication in the gut-associated lymphatic tissue, including intestinal Peyer's patches, followed by extensive infection of lymphatic organs, including thymus and circulating lymphocytes. Moreover, T cells were selectively depleted. Thus, CDV takes advantage of mucosal surfaces for host invasion and lymphocytes for swift dissemination. A CDV unable to recognize the signaling lymphocytic activation molecule (SLAM [CD150]) that is expressed in lymphocytes and other immune cells did not spread. A V-defective CDV multiplied with reduced efficiency in lymphocytes and did not inhibit the interferon and cytokine responses. Protein C affected the severity of rash and digestive symptoms elicited by V-defective CDV, but it was dispensable for the invasion of the lymphatic organs. These findings prove formally that SLAM recognition is necessary for morbillivirus virulence. They also reveal how two viral proteins affect pathogenesis: V sustains the swift lymphocyte-based invasion of mucosal tissue and lymphatic organs, whereas C sustains subsequent infection phases.

Specific alteration of the expression of selected hypothalamic neuropeptides during acute and late mouse brain infection using a morbillivirus: relevance to the late-onset obesity?

Neurotropic viruses are involved in pathologies of the central nervous system, triggering transient or irreversible disorders, such as neurological diseases or homeostasis imbalance. In experimental animals, viruses have been shown to cause obesity, a complex disease depending on multiple factors, including genetic susceptibility and environmental components. Using a mouse model of virally induced obesity following brain infection by the Canine Distemper Virus (CDV), a morbillivirus closely related to the human measles virus, we investigated the modulation of expression of several hypothalamic neuropeptides known to intervene in the regulation of body weight and energy expenditure, both during the acute and late stages of infection. During the acute stage, while viral replication occurs, we found a dramatic decrease of expressions of neuropeptides, in particular neuropeptide Y, melanin-concentrating hormone (MCH), hypocretin, vasopressin and tachykinins, the magnitude of which seemed to be linked to the viral burden and the individual susceptibility. The effect of the virus, however, varied with the hypothalamic nucleus and neuropeptide involved, suggesting that certain circuits were affected while others remained intact. During the late stage of infection, marked recovery to the initial hypothalamic levels of peptide expression was seen in a number of lean animals, suggesting recovery of homeostasis equilibrium. Interestingly, some neuropeptidergic systems remained disturbed in mice exhibiting obese phenotype, arguing for their involvement in triggering/maintaining obesity. Even though our data could not fully explain the viral-induced obesity, they may be helpful in understanding the molecular events associated with obesity and in investigating therapeutic alternatives.

Morbillivirus infections in aquatic mammals.

Morbillivirus infections which were not documented in aquatic mammals until 1988, have caused at least five epizootics in these species during the last 10 years. Affected populations include European harbour seals (Phoca vitulina) and grey seals (Halichoerus grypus) in 1998, Baikal seals (Phoca siberica) in Siberia from 1987-1988, striped dolphins (Stenella coeruleoalba) in the Mediterranean Sea from 1990-1992 and bottlenose dolphins (Tursiops truncatus) along the eastern coast of the United States from 1987-1988 and in the Gulf of Mexico from 1993-1994. Clinical signs and lesions in affected animals were similar to those of canine distemper. Lesions were mainly seen in lung, central nervous and lymphoid tissues and included formation of intranuclear and intracytoplasmic inclusion bodies. Syncytia were commonly found in lung and lymphoid tissues of cetaceans but not of pinnipeds. Antigenic and molecular biological studies indicate that a newly discovered morbillivirus, termed phocine distemper virus, and canine distemper virus were responsible for recent pinniped epizootics; cetacean die-offs were caused by strains of a second, newly recognized cetacean morbillivirus. Serological evidence of morbillivirus infection has been identified in a broad range of marine mammal populations and recent epizootics probably resulted from transfer of virus to immunologically-naive populations.

Diseases and environmental contaminants in seals from the Baltic and the Swedish west coast.

Investigations have shown that Baltic grey seal (Halichoerus grypus) and ringed seal (Phoca hispida) suffer from a disease complex described as a primary lesion in the adrenals causing secondary reactions in various other organs. Studies on historical Baltic grey seal skull bone material show that the prevalence of affected animals started to increase after World War II. The disease complex explains the dramatic decrease in the Baltic grey and ringed seal population during the 1960s and 1970s and is believed to be caused by environmental pollutants. In 1988, about 60% of the harbor seal population (Phoca vitulina) along the Swedish west coast and in the southwestern part of the Baltic died in the PDV epizootic (Phocine Distemper Virus). Whether the course of the epizootic was altered by environmental pollutants is still an open question. Studies on historical harbor seal skull bone material from both the Baltic and the Swedish west coast show that the incidence of skull bone lesions has also increased in these populations since World War II, indicating the presence of unnatural stress factors. After the epizootic, the harbor seal populations both in the Baltic and along the Swedish west coast have increased in number. Chemical analysis of tissues has been performed on the three seal species collected in various areas of the Baltic and the Swedish west coast. The concentrations of 17 metals and non-metal elements, sDDT and PCBs, DDE and PCB methylsulfones, toxaphene, chlordanes, polybrominated diphenyl ethers, PCDDs and PCDFs have been determined in selected groups of seals in order to determine spatial, species and age variations in concentrations. Furthermore, healthy animals have been compared to diseased animals. Spatial variation was found mostly within the group of organohalogenated compounds, a group of contaminants where a strong covariation between the various compounds was also found. On the basis of the analytical results as well as the pathological findings on Baltic seals, the group of DDE and PCB methyl sulfones is tentatively suggested to be more important in explaining the disease complex than coplanar structures including dioxins.

Abnormally high polychlorinated biphenyl levels in striped dolphins (Stenella coeruleoalba) affected by the 1990-1992 Mediterranean epizootic.

PCB concentrations and total lipid content were determined in the blubber and liver of striped dolphins affected by the 1990 morbillivirus epizootic in the Mediterranean Sea, and in the blubber of striped dolphins from the same area sampled with a biopsy dart in 1987-1989 and 1991. PCB levels were found to be significantly higher in the individuals that succumbed to the epizootic than in the 'healthy' population sampled before or after the event. Although recent mobilization of lipid reserves was found to have occurred in some of the diseased dolphins, this had little effect on their PCB blubber concentrations and cannot explain the observed difference with the healthy individuals. Three hypotheses are put forward to explain the apparent link between high PCB levels and mortality caused by the epizootic: (i) depressed immunocompetence caused by PCBs leading to an increase in individual susceptibility to the morbillivirus infection, (ii) mobilization of fat reserves leading to increased PCB levels in blood which, in turn, may produce a liver lesion capable of increasing the individual's susceptibility to the morbillivirus infection, and (iii) previous existence of an unspecific hepatic lesion producing impairment of the liver function which, in turn, could lead to an increase both in tissue PCB concentrations and in individual susceptibility to the morbillivirus infection.