R
Anton Sebastian in A Dictionary of the History of Medicine, 2018
Rabies [Latin: rabere, to rage] George Gottfried Zinke of Jena proposed that the saliva of the rabid dog was infectious in 1804. This remained unproved until 1879, when Victor Galtier (1846–1908) of Paris managed to produce a paralytic form of rabies in rabbits by inoculating them with infective material. Curare was used to relax the muscles in patients with rabies in 1838. Changes in the central nervous system were reported by Louis Pasteur (1822–1895) and colleagues in 1881, and the first inoculation with antirabies vaccine was performed by him on July 6 1885. Negri bodies, characteristic cell inclusions, were observed by Italian microbiologist, Adelchi Negri (1867–1912) in 1903, but he mistook them for parasitic protozoal organisms. See hydrophobia.
The nervous system and the eye
C. Simon Herrington in Muir's Textbook of Pathology, 2020
Rabies remains a major problem in many countries. Most human cases follow the bite of a rabid dog although the major reservoirs are the fox, skunk and jackal. The rhabdovirus enters the body from the saliva and reaches the CNS by retrograde transport along peripheral nerves from the bite. The incubation of the disease varies according to the distance of the bite from the CNS; sometimes it is as short as 2 weeks but more commonly is 13 months or even longer. As the old name of hydrophobia implies, spasm of the muscles of swallowing on attempting to drink water may be an early symptom. The pathognomonic histological feature is the Negri body, an intracytoplasmic inclusion 1–7 μm in diameter, within which virus can be identified.
Rabies Virus Neurovirulence
Sunit K. Singh, Daniel Růžek in Neuroviral Infections, 2013
The histopathological changes are also mild and mostly related to inflammatory processes. Some degree of inflammatory cell infiltration is normally present, principally involving lymphocytes and monocytes, accompanied by some plasma cells. However, in cases with intense inflammation, the infiltrate is predominantly composed of neutrophils (Perl and Good 1991). In the majority of rabies cases, perivascular cuffing can be seen whereby mononuclear inflammatory cells form accumulations around vessels, mostly in the gray matter of the spinal cord and brain (Hicks et al. 2009). Excessive proliferation of the neuroglial supportive tissue (gliosis), along with accumulations of activated microglia (Babes’ nodules) can also be seen in many infections (Rossiter and Jackson 2007). These pathological alterations are not unique for rabies and the occurrence, density, and distribution can be highly variable between the differing forms, and individual cases of disease (Rossiter and Jackson 2007). There have also been fatal cases of rabies where virtually no inflammatory changes were observed (Hicks et al. 2009). One change that is often observed, which distinguishes rabies infection from other viral encephalitides, is the intracytoplasmic inclusions named “Negri bodies.” These are thought to be large aggregations of viral N and P proteins and have been implicated as possible specialized sites for viral transcription and replication (Lahaye et al. 2009). These markers of infection have been observed in many different regions of the CNS and their presence and distribution can be influenced by a range of host and virus factors including virus strain, host species, and the clinical phase of disease.
Modern biologics for rabies prophylaxis and the elimination of human cases mediated by dogs
Published in Expert Opinion on Biological Therapy, 2020
Terapong Tantawichien, Charles E. Rupprecht
Taxonomically, rabies is caused by highly neurotropic, rod-shaped, enveloped, single-stranded, negative-sense RNA viruses, within the Family Rhabdoviridae, Genus Lyssavirus (Figure 1). As with other genera within the family, lyssaviruses form a monophyletic clade, based upon phylogenetic analyses and all viral species have a similar morphology, genome, and replication strategy [5]. The inner, viral nucleoprotein (N) is tightly associated with RNA to form a helical capsid, containing anti-genomic RNA, generated during replication and serving as a template for synthesis of complexes with genomic RNA. During translation, the capped and polyadenylated mRNAs are transcribed from each gene (i.e., in the 3′ to 5′ direction). The five primary viral proteins have multiple structural and functional roles. The viral phosphoprotein (P) is an essential replication co-factor. The P protein interacts with the N protein. Both are associated with genomic RNA and the viral RNA-dependent RNA polymerase (L protein), to form a viral ribonucleoprotein (RNP) complex. Within neurons, the viral RNP, with an abundance of N protein, contributes to intracytoplasmic inclusions (i.e., Negri bodies). Negri bodies are of historical diagnostic importance, representative of compartmentalized viral replication and assembly [6]. In addition, the P protein is a primary interferon (IFN) antagonist, targeting IFN induction [7]. The matrix (M) protein maintains structural features between the inner and outer viral proteins. In addition, the M protein has a role in viral replication and assembly. Together with the P protein, the M protein is involved in the process of evading innate immune responses by regulation of cell signaling [8]. The outer glycoprotein (G) mediates attachment to host receptors (such as the neuronal cell adhesion molecule and p75NTR, among others) and fusion between viral and endosomal membranes, with viral genome release into the cytoplasm of the cell [9,10]. The detection of G protein by the host leads to the formation of virus-neutralizing antibodies (VNA), as the primary immune effector. Besides a primary role in RNA synthesis, the L protein is also involved in mRNA capping and transcriptional initiation [11].
Related Knowledge Centers
- Cerebellum
- Cytoplasm
- Eosinophilic
- Inclusion Bodies
- Purkinje Cell
- Pyramidal Cell
- Rabies Virus
- Hippocampus
- Pathognomonic
- Neuron