Molecular signatures in cetacean morbillivirus and host species proteomes: Unveiling the evolutionary dynamics of an enigmatic pathogen?

Cetacean morbillivirus (CeMV) infects marine mammals often causing a fatal respiratory and neurological disease. Recently, CeMV has expanded its geographic and host species range, with cases being reported worldwide among dolphins, whales, seals, and other aquatic mammalian species, and therefore has emerged as the most threatening nonanthropogenic factor affecting marine mammal's health and conservation. Extensive research efforts have aimed to understand CeMV epidemiology and ecology, however, the molecular mechanisms underlying its transmission and pathogenesis are still poorly understood. In particular, the field suffers from a knowledge gap on the structural and functional properties of CeMV proteins and their host interactors. Nevertheless, the body of scientific literature produced in recent years has inaugurated new investigational trends, driving future directions in CeMV molecular research. In this mini-review, the most recent literature has been summarized in the context of such research trends, and categorized into four priority research topics, such as (1) the interaction between CeMV glycoprotein and its host cell receptors across several species; (2) the CeMV molecular determinants responsible for different disease phenotype; (3) the host molecular determinants responsible for differential susceptibility to CeMV infection; (4) the CeMV molecular determinants responsible for difference virulence among circulating CeMV strains. Arguably, these are the most urgent topics that need to be investigated and that most promisingly will help to shed light on the details of CeMV evolutionary dynamics in the immediate future.

Cetacean Morbillivirus and Toxoplasma gondii Co-infection in Mediterranean Monk Seal Pup, Italy.

A Mediterranean monk seal (Monachus monachus) pup from the southern Adriatic coast of Italy showed cetacean morbillivirus (CeMV) and disseminated Toxoplasma gondii co-infection, which probably resulted from CeMV-induced immunosuppression. These findings are of concern for the conservation of this critically endangered species.

Retrospective immunohistochemical investigation on dolphin morbillivirus infection by comparing the performance of heterologous monoclonal and polyclonal antibodies - Short communication.

Dolphin morbillivirus (DMV) is a pathogen of great concern in free-ranging cetaceans. Confirmation and staging of morbillivirus infections rely on histology and immunohistochemistry (IHC), following molecular detection. As at the present time no specific antibodies (Abs) against DMV are available, two heterologous Abs have been used worldwide for the examinations of morbillivirus infections of cetaceans. One is a monoclonal Ab (MoAb) prepared against the N protein of canine distemper virus (CDV), whereas the other is a polyclonal Ab raised in rabbits against rinderpest virus (RPV). Both Abs are known to show cross-reactivity with DMV. In this study we compared the labelling quality and the neuroanatomical distribution of staining with these two Abs by means of IHC analysis. To this end, serial sections of the target organs from ten free-ranging stranded cetaceans, previously diagnosed as being infected with DMV by PCR and/or serology, were subjected to IHC. The brain, lungs and lymph nodes of one animal were found to be positive with both Abs. From two other animals, the brain and the spleen, respectively, tested positive only with the polyclonal Ab. In the positive brain tissues, multifocal immunostaining was observed, with similar staining location and extent, with the two antibodies tested. Our results suggest that the polyclonal anti-RPV Ab might have a stronger binding activity to DMV than the anti-CDV MoAb. Nevertheless, the elaboration and use of specific anti-DMV Abs might be essential to guarantee conclusive results in diagnostic and pathogenetic investigations.

Dolphin Morbillivirus in Eurasian Otters, Italy.

We report biomolecular evidence of dolphin morbillivirus in 4 wild Eurasian otters (Lutra lutra) from southern Italy; 2 animals showed simultaneous immunohistochemical reactivity against morbilliviral antigen. These cases add further concern and support to the progressively expanding host range of dolphin morbillivirus in the western Mediterranean Sea.

Novel dolphin morbillivirus (DMV) outbreak among Mediterranean striped dolphins Stenella coeruleoalba in Italian waters.

An unusual mortality event (UME) of striped dolphins Stenella coeruleoalba occurred in the period July to December 2016 along the Italian Ionian coastline. We conducted a complete postmortem examination on 28 specimens and detected dolphin morbillivirus (DMV), by means of biomolecular analyses, in the target tissues of 17 animals. Unlike previous outbreaks occurring in the Mediterranean Sea in 2011 and 2013, we observed typical pathological changes suggestive of morbilliviral infection in an acute/subacute phase and immunohistochemical reactivity. The same findings were observed in 13 other specimens beached along the Italian coastline during 2016 with no temporal and geographical relationship with the ongoing epidemic outbreak. Molecular characterization and phylogenetic analysis showed that DMV sequences detected in Italy in 2016 clustered with those identified in Portugal and Galicia (Spain), representing a novel DMV strain of Atlantic origin which entered the Mediterranean Sea and affected a naïve striped dolphin population. DMV sequences detected in the previous Mediterranean outbreaks exhibited a marked genetic relatedness and diverged from those detected in cetaceans stranded along the Galician and Portuguese coasts since 2007.

Occlusive mycotic tracheobronchitis and systemic Alphaherpesvirus coinfection in a free-living striped dolphin Stenella coeruleoalba in Italy.

A juvenile female striped dolphin Stenella coeruleoalba live stranded on 4 March 2016 at Alassio, western Ligurian Sea coast, Italy. The dolphin died shortly after stranding, and a complete postmortem examination was performed. Necropsy revealed severe tracheal occlusion and unilateral bronchial stenosis with luminal accumulation of abundant green-yellow mucous-gelatinous material. Histological features suggestive of tracheobronchial aspergillosis were observed. Cultures of lung tissue and tracheo-bronchial exudate isolated Aspergillus fumigatus, identified by a Microseq D2 LSUrDNA fungal sequencing kit. A pan-Herpesvirus nested-PCR assay on frozen samples obtained from multiple organs was positive. Phylogenetic analysis on the partial DNA polymerase gene revealed that the striped dolphin isolate was closely related to known cetacean Alphaherpesvirus sequences from the same host species. Attempted virus isolation was unsuccessful. The tissue levels of different persistent organic pollutants and the toxicological stress, evaluated using a theoretical model, showed a severely impaired immune response. This study reports the first case of occlusive mycotic tracheobronchitis in a free-living cetacean and the first molecular identification of an Alphaherpesvirus in a free-ranging striped dolphin stranded on the coast of Italy.

Dolphin Morbillivirus Associated with a Mass Stranding of Sperm Whales, Italy.

In September 2014, seven sperm whales were stranded along Italy's Adriatic coastline. Postmortem investigations on 3 female adult whales and 1 male fetus carried by the largest female revealed molecular and immunohistochemical evidence of dolphin morbillivirus infection. A possible role of the virus in the stranding event was considered.

Mediterranean Fin Whales (Balaenoptera physalus) Threatened by Dolphin MorbilliVirus.

During 2011-2013, dolphin morbillivirus was molecularly identified in 4 stranded fin whales from the Mediterranean Sea. Nucleoprotein, phosphoprotein, and hemagglutinin gene sequences of the identified strain were highly homologous with those of a morbillivirus that caused a 2006-2007 epidemic in the Mediterranean. Dolphin morbillivirus represents a serious threat for fin whales.

Meningoencephalitis and Listeria monocytogenes, Toxoplasma gondii and Brucella spp. coinfection in a dolphin in Italy.

Listeria monocytogenes, Toxoplasma gondii and Brucella spp. can infect a wide range of species, including humans. In cetaceans, meningoencephalitis has been associated with T. gondii and Brucella spp. infection, whereas to our knowledge, L. monocytogenes infection has not previously been reported. Meningoencephalitis and L. monocytogenes, T. gondii and Brucella spp. were identified by means of both direct and indirect laboratory techniques in an adult female striped dolphin Stenella coeruleoalba found stranded in January 2015 on the Ligurian Sea coast, northwestern Italy. The animal was emaciated, and histopathology disclosed severe meningoencephalitis. The nature of the inflammatory response and intra-lesional protozoa were consistent with a mixed infection by L. monocytogenes, T. gondii and Brucella spp. We believe this is an unprecedented case of infection by 3 zoonotic pathogens and also the first bacteriologically confirmed case report of neurolisteriosis in cetaceans. Cerebral toxoplasmosis and neurobrucellosis may have led to the animal's disorientation and stranding, with L. monocytogenes having likely exacerbated the coinfection leading to the demise of this dolphin.

Role of palatine tonsils as a prion entry site in classical and atypical experimental sheep scrapie.

Atypical and classical scrapie-infected sheep brain tissue was monolaterally injected into the tonsils of lambs to investigate their role as a prion entry point. We first detected classical PrP(Sc) within the inoculated tonsil and in the ipsilateral retropharyngeal lymph node at 3 months postinoculation (p.i.). At 7 months p.i., PrP(Sc) colonized other lymphoid tissues bilaterally, including ileal Peyer's patches. The earliest PrP(Sc) deposition within the brain was ipsilaterally observed at 9 months p.i. in the substantia reticularis of the medulla oblongata. At 12 months p.i., PrP(Sc) deposition was present bilaterally in the nucleus parasympathicus nervi vagi, as well as in the intermediolateral cell column of the thoracolumbar spinal cord. No PrP(Sc) was detected in the lambs inoculated with atypical scrapie. These findings suggest that neuroinvasion may naturally occur from the tonsil after a widespread prion replication within the lymphoid tissues during classical scrapie only, thus mimicking the pathogenesis after oral ingestion.

Cetacean strandings in Italy: an unusual mortality event along the Tyrrhenian Sea coast in 2013.

An unusual mortality event involving cetaceans, mainly striped dolphins Stenella coeruleoalba (Meyen, 1833), occurred along the Tyrrhenian Sea coast of Italy during the first 3 mo of 2013. Based on post-mortem analyses carried out according to body condition on 66 dolphins (54% of stranded animals), several hypotheses to explain the causes of this mortality event were proposed. Although no definitive conclusions can be drawn, dolphin morbillivirus was deemed the most likely cause, although other infectious agents (including Photobacterium damselae damselae and herpesvirus) or environmental factors may also have contributed to this recent mortality event.

Measles Virus-Induced Immune Amnesia and SARS-CoV-2 Evolution.

An interesting article recently published in Science Translational Medicine reports a variable risk of persistent COVID-19 among patients affected by different immunodeficiency conditions [...].

Dolphin morbillivirus infection in a captive harbor seal (Phoca vitulina).

During the second morbillivirus epidemic (2007 to 2011) in cetaceans along the Italian coastline, dolphin morbillivirus (DMV) was detected by molecular analyses in a captive harbor seal (Phoca vitulina), with pathological findings consistent with morbillivirus infection. This report confirms interspecies DMV transmission from cetaceans to pinnipeds.

The SARS-CoV-2 Pandemic at the Wildlife-Domestic Animal-Human Interface.

Since the start of the COVID-19 pandemic, which has hitherto killed almost 7 million people worldwide-although the true mortality figures could be much higher-we have witnessed a progressively expanding number of domestic and wild mammalian species acquiring Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection, both spontaneously and experimentally [...].

Tsunami-Driven Spread of Toxoplasma gondii and Other Microbial Pathogens: Implications for Cetacean Health and Conservation.

Six years have now gone by since Dr James T [...].

Alien Crabs as Potential Hosts of Pathogens Impacting Marine Megafauna's Health and Conservation.

Climate change, with a special emphasis on global warming, is believed to be a key driver of the accelerated rate of alien species expansion into the Mediterranean Sea basin and, more generally, into all marine and oceanic ecosystems [...].

Flood-Associated, Land-to-Sea Pathogens' Transfer: A One Health Perspective.

Similarly to many other countries across the globe, several floods have been recorded in Italy throughout the last few decades, including those of catastrophic magnitude that occurred in the Emilia-Romagna and Tuscany regions last May and a few weeks ago, respectively [...].