Intranuclear inclusions in paramyxovirus-induced encephalitis: evidence for altered nuclear body differentiation

Abstract

Intranuclear inclusion bodies (INB) are frequently encountered in viral infections, where they are thought to be accumulations of viral particles. However, for RNA viruses replicating in the cytoplasm, this compartmentalization represents a paradox not consistent with the viral replication cycle. To define the basis for intranuclear paramyxoviral inclusion bodies in astrocytes, natural cases of canine distemper virus subacute encephalitis were examined by light and transmission electron microscopy, and by quantitative confocal immunofluorescence microscopy. Although INB were viral antigen positive, they were not composed of structurally recognizable paramyxoviral nucleocapsids. The structural basis for the INB was instead viral antigen-associated forms of nucleolar development known as nuclear bodies. Three variants of the light microscopic Cowdry type A INB were complex nuclear bodies, giant beaded nuclear bodies (sphaeridia), and nuclear body-associated granulofilamentous matrices. In the latter, the granulofilamentous matrix frequently filled the nucleus, resulting in a fourth morphological INB variant, and was associated with morphological evidence of nuclear degeneration. These findings suggest a novel mechanism of virus-induced cytopathology whereby intranuclear viral protein exerts deleterious effects upon nucleolar differentiation in infected cells and hence altered host cell RNA metabolism.

Rational Attenuation of a Morbillivirus by Modulating the Activity of the RNA-Dependent RNA Polymerase

“…Many positive stranded RNA viruses extensively modify and utilize membranes to facilitate their replication, and these have been suggested to represent topologically and functionally related structures (43). Although large intracytoplasmic inclusions are a feature of most paramyxovirus infections and these are generally considered to be the sites of virus replication, membrane rearrangements or vesiculation do not seem to be closely associated with these eosinophilic dense aggregates of viral nucleocapsid (36). We are currently extending these observations by using real-time confocal microscopy to examine the dynamics of the intracellular trafficking of both incoming and newly synthesized polymerases in order to better understand virus assembly and release.…”

Neuronal Storage Disease in a Group of Captive Humboldt Penguins (Spheniscus humboldti)

“…The ultrathin sections were examined using a Philips 300 transmission electron microscope as previously described. 15 TEM revealed that the perikarya of neurons were distended by fairly uniform vacuoles that contained whorled layers of alternating dense and pale material ( multilayered concentric lamellar bodies ; Fig. 3).…”