Comparative histopathologic and viral immunohistochemical studies on CeMV infection among Western Mediterranean, Northeast-Central, and Southwestern Atlantic cetaceans

Abstract

Cetacean morbillivirus (CeMV) is a major natural cause of morbidity and mortality in cetaceans worldwide and results in epidemic and endemic fatalities. The pathogenesis of CeMV has not been fully elucidated, and questions remain regarding tissue tropism and the mechanisms of immunosuppression. We compared the histopathologic and viral immunohistochemical features in molecularly confirmed CeMV-infected Guiana dolphins (Sotalia guianensis) from the Southwestern Atlantic (Brazil) and striped dolphins (Stenella coeruleoalba) and bottlenose dolphins (Tursiops truncatus) from the Northeast-Central Atlantic (Canary Islands, Spain) and the Western Mediterranean Sea (Italy). Major emphasis was placed on the central nervous system (CNS), including neuroanatomical distribution of lesions, and the lymphoid system and lung were also examined. Eleven Guiana dolphins, 13 striped dolphins, and 3 bottlenose dolphins were selected by defined criteria. CeMV infections showed a remarkable neurotropism in striped dolphins and bottlenose dolphins, while this was a rare feature in CeMV-infected Guiana dolphins. Neuroanatomical distribution of lesions in dolphins stranded in the Canary Islands revealed a consistent involvement of the cerebrum, thalamus, and cerebellum, followed by caudal brainstem and spinal cord. In most cases, Guiana dolphins had more severe lung lesions. The lymphoid system was involved in all three species, with consistent lymphoid depletion. Multinucleate giant cells/syncytia and characteristic viral inclusion bodies were variably observed in these organs. Overall, there was widespread lymphohistiocytic, epithelial, and neuronal/neuroglial viral antigen immunolabeling with some individual, host species, and CeMV strain differences. Preexisting and opportunistic infections were common, particularly endoparasitism, followed by bacterial, fungal, and viral infections. These results contribute to understanding CeMV infections in susceptible cetacean hosts in relation to factors such as CeMV strains and geographic locations, thereby establishing the basis for future neuro- and immunopathological comparative investigations.

Comparative Immunopathology of Cetacean morbillivirus Infection in Free-Ranging Dolphins From Western Mediterranean, Northeast-Central, and Southwestern Atlantic

“…Repopulation and germinal center formation in lymphoid tissues from persistently infected and convalescent hosts are common in this stage ( 5 , 6 ). Detection of such “persistently infected” and/or “convalescent” dolphins is complicated; however, we observed similar regenerative findings in several cases from the Canary Islands and the Mediterranean Sea largely involving those animals with chronic systemic and chronic localized “brain only forms” of CeMV infection [supported by IHC and PCR results [data published elsewhere]] ( 1 , 14 ). These changes were characterized by follicular, paracortical, and medullary cord expansion (reactive hyperplasia), typically encompassing distorted or poorly delineated lymphocytic growths including T cells and B cells accompanied by slightly increased numbers of IgG+ cells.…”

“…For immunophenotypic characterization of local inflammatory cell populations, the number of immunopositive cells was semiquantitatively evaluated for each marker in lymphoid (lymph nodes, spleen), lung, and CNS tissues according to following score: –, no; +, <10%; ++, 10–50%; +++, 51–90%, and ++++, >90% immunopositive cells, in 10 high-power (400x) fields. The histo-anatomical compartments analyzed were: lymph nodes (primary and secondary follicles, paracortex, medullary cords and cortical, paracortical, and medullary sinuses; afferent/efferent lymphatics); spleen (follicles, perifollicular zone, periarteriolar lymphoid sheath [PALS], red pulp sinuses, and cords); lung (bronchial/bronchiolar mucosa and submucosa including glands and associated lymphoid tissue [BALT]; alveolar spaces and septa; interstitium; pleura; vasculature including lymphatics); brain (cerebral cortex, cerebellum, brain stem, spinal cord) ( 13 , 14 ). Additionally, IHC expression intensity was subjectively scored (increasing intensity) as 1, 2, and 3.…”

Histopathological Differential Diagnosis of Meningoencephalitis in Cetaceans: Morbillivirus, Herpesvirus, Toxoplasma gondii, Brucella sp., and Nasitrema sp.

“…CeMVs are RNA viruses responsible for massive dieoffs worldwide and include three well-characterized strains (porpoise morbillivirus, DMV, and PWMV) and three less wellcharacterized strains detected in Hawaii and in the southern hemisphere (32). CeMV is a well-recognized neurotropic pathogen and localized brain lesions have been described in cetaceans that have cleared systemic CeMV infection, resembling subacute sclerosing panencephalitis (SSPE) and old dog encephalitis (ODE) (20,32,65). IHC labeling has been successfully used to diagnose CeMV preferentially in earlier stages of the disease.…”

Neurobrucellosis in a common bottlenose dolphin (Tursiops truncatus) stranded in the Canary Islands

“…The cerebrum also showed satellitosis, glial degeneration and necrosis, rarefaction/liquefactive necrosis, and vasculitis; the brainstem (pons) presented spongiosis and Wallerian degeneration; and the spinal cord showed evidence of glial nodules, white matter spongiosis and polyrradiculoneuritis. Finally, marked, multifocal, chronic lymphohistiocytic cranial neuritis, and meningitis and neurohypophisitis were present [42]. However – despite the severe non-suppurative meningitis (with more than 20 layers of histiocytic and lymphocytic cells), encephalomyelitis, and perineuritis in the CNS (Fig.…”