scholarly journals Molecular Mechanisms of Raccoon Rabies Virus Progression in Its Natural Host

2014 ◽  
Vol 04 (16) ◽  
pp. 1222-1236
Author(s):  
Vythegi Srithayakumar ◽  
Hariharan Sribalachandran ◽  
Rick Rosatte ◽  
Christopher J. Kyle
Keyword(s):  
Rabies Virus ◽  
Molecular Mechanisms ◽  
Natural Host ◽  
Raccoon Rabies Virus

scholarly journals Change in the Single Amino Acid Site 83 in Rabies Virus Glycoprotein Enhances the BBB Permeability and Reduces Viral Pathogenicity

2021 ◽  
Vol 8 ◽  
Author(s):  
Chunfu Li ◽  
Yongzhi Wang ◽  
Huiting Liu ◽  
Xinghua Zhang ◽  
Dalai Baolige ◽  
...  
Keyword(s):  
Amino Acid ◽  
G Protein ◽  
Rabies Virus ◽  
Cell Cultures ◽  
Molecular Mechanisms ◽  
Single Amino Acid ◽  
Wild Type ◽  
Cellular Adaptation ◽  
Adult Mice ◽  
Bbb Permeability

Lab-attenuated rabies virus (RABV) is a highly cellular adaptation and less pathogenic than wild-type RABV. However, the molecular mechanisms that regulate the cellular adaptation and pathogenicity remain obscure. In this work, we isolated a wild-type RABV (CNIM1701) from a rabid bovine in northern China. The original CNIM1701 was lethal in adult mice and restricted replication in cell cultures. After 20 serial passages in the brains of suckling mice, the virus was renamed CNIM1701-P20, which was safe in adult mice and replicated well in cell cultures. In addition, sequence comparison analysis of the original CNIM1701 and CNIM1701-P20 identified 2 amino acid substitutions on G protein (Lys83 → Arg83 and Pro367 → Ser 367) related to pathogenesis and cellular adaptation. Using site-directed mutagenesis to exchange Lys83 with Arg83 and Pro367 with Ser 367 in the G protein of the RABV SAD strain, the pathogenicity of rSAD-K83R was significantly decreased. Our data indicate that the decreased pathogenicity of rSAD-K83R is due to increasing the expression of RABV-G, which also induced a higher level of apoptosis in infected cells. Furthermore, the K83 mutation induced high expression of MMP-2 and MMP-9 on DCs and promoted blood–brain barrier (BBB) permeability. These results demonstrate that the pathogenesis of RABV is partially dependent on G expression and BBB permeability, which may help in the design and development of highly safe, live-RABV vaccines.

scholarly journals Origin of 3 Rabid Terrestrial Animals in Raccoon Rabies Virus–Free Zone, Long Island, New York, USA, 2016–2017

2020 ◽  
Vol 26 (6) ◽  
Author(s):  
Scott Brunt ◽  
Heather Solomon ◽  
Hilaire Leavitt ◽  
Erica Lasek-Nesselquist ◽  
Pascal LaPierre ◽  
...  
Keyword(s):  
New York ◽  
Rabies Virus ◽  
Long Island ◽  
Free Zone ◽  
Raccoon Rabies Virus

scholarly journals Clinicopathologic Variation in Raccoons Infected with Different Street Rabies Virus Isolates

1996 ◽  
Vol 8 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Amir N. Hamir ◽  
Gale Moser ◽  
Charles E. Rupprecht
Keyword(s):  
Brain Stem ◽  
Rabies Virus ◽  
Latin American ◽  
Ganglion Cells ◽  
Clinical Signs ◽  
Natural Case ◽  
Group 2 ◽  
Raccoon Rabies Virus ◽  
Random Groups ◽  
Group 1

Ten raccoons were divided into two random groups (groups 1 and 2) of five animals each. Group 1 raccoons were inoculated intramuscularly in the masseter muscle with a raccoon rabies virus isolate obtained from a natural case of raccoon rabies from the northeastern USA. Group 2 raccoons were infected by a similar route with a Latin American canine isolate of rabies virus. Raccoons either died suddenly or developed neurologic signs compatible with rabies. Clinical signs of rabies in group 1 raccoons were more severe than in group 2. Raccoons in group 1 either died acutely or were euthanized within 25 days (x ± SD = 20.6 ± 2.7 days) postinfection, whereas all group 2 raccoons showed neurologic signs and were euthanized within 17 days (14.2 ± 2.2 days) postinfection. Light microscopic findings revealed extensive nonsuppurative encephalitis predominantly located in the cerebrum and brain stem of raccoons in group 1, whereas in group 2 raccoons the lesions were confined to the brain stem regions. In group 1 raccoons, Negri bodies were commonly seen on hematoxylin and eosin (HE)-stained sections of brain and in ganglion cells of 5 other tissues (trigeminal nerve, salivary glands, duodenum, pancreas, adrenal gland). Negri bodies, however, were either absent or were only occasionally observed in corresponding tissues of raccoons infected with the canine strain (group 2). Paraffin-embedded tissue sections were also examined for Negri bodies by an immunoperoxidase test, which revealed results similar to the HE findings. Results of this study are compared with histopathologic and immunohistochemical findings in raccoons naturally infected with rabies.

scholarly journals Neuropathology and diagnostic features of rabies in a litter of piglets, with a brief review of the literature

2020 ◽  
Vol 32 (1) ◽  
pp. 166-168
Author(s):  
Christopher L. Siepker ◽  
Martha F. Dalton ◽  
Brittany J. McHale ◽  
Kaori Sakamoto ◽  
Daniel R. Rissi
Keyword(s):  
United States ◽  
Rabies Virus ◽  
Fluorescent Antibody ◽  
Antibody Test ◽  
Medial Lemniscus ◽  
Eastern United States ◽  
Diagnostic Features ◽  
Neuronal Necrosis ◽  
Raccoon Rabies Virus ◽  
Viral Inclusions

Porcine rabies is exceedingly rare worldwide. We describe herein the neuropathology and the diagnostic features of an outbreak of rabies in a litter of piglets attacked by a skunk in Georgia, United States. Rabies viral infection was confirmed in 2 of 3 piglets submitted for testing. Inflammatory and degenerative changes were more prominent in the brainstem and consisted of lymphoplasmacytic meningoencephalitis with glial nodules, neuronal necrosis, and neuronophagia. No viral inclusions (Negri bodies) were observed in multiple sections of brain. A fluorescent antibody test on fresh samples of brainstem and cerebellum was confirmatory for the eastern United States raccoon rabies virus variant. Immunoreactivity for rabies virus was detected across all brain sections in both cases but was more prominent in the thalamic and brainstem nuclei, as well as in the medial lemniscus. Rabies is an important differential diagnosis in pigs with neurologic disease.

scholarly journals Molecular Basis of Neurovirulence of Flury Rabies Virus Vaccine Strains: Importance of the Polymerase and the Glycoprotein R333Q Mutation

2010 ◽  
Vol 84 (17) ◽  
pp. 8926-8936 ◽  
Author(s):  
Lihong Tao ◽  
Jinying Ge ◽  
Xijun Wang ◽  
Hongyue Zhai ◽  
Tao Hua ◽  
...  
Keyword(s):  
Cell Culture ◽  
Rabies Virus ◽  
Genetic Stability ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Rabies Vaccine ◽  
Glycoprotein G ◽  
Attenuation Mechanism ◽  
Significant Attenuation ◽  
Stability Enhancement

ABSTRACT The molecular mechanisms associated with rabies virus (RV) virulence are not fully understood. In this study, the RV Flury low-egg-passage (LEP) and high-egg-passage (HEP) strains were used as models to explore the attenuation mechanism of RV. The results of our studies confirmed that the R333Q mutation in the glycoprotein (GR333Q) is crucial for the attenuation of Flury RV in mice. The R333Q mutation is stably maintained in the HEP genome background but not in the LEP genome background during replication in mouse brain tissue or cell culture. Further investigation using chimeric viruses revealed that the polymerase L gene determines the genetic stability of the GR333Q mutation during replication. Moreover, a recombinant RV containing the LEP G protein with the R333Q mutation and the HEP L gene showed significant attenuation, genetic stability, enhancement of apoptosis, and immunogenicity. These results indicate that attenuation of the RV Flury strain results from the coevolution of G and L elements and provide important information for the generation of safer and more effective modified live rabies vaccine.

Rabies virus matrix protein targets host actin cytoskeleton: A Protein-Protein interaction analysis

2020 ◽  
Author(s):  
Fatemeh Zandi ◽  
Vahid Khalaj ◽  
Fatemeh Goshadrou ◽  
Anna Meyfour ◽  
Alireza Gholami ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Matrix Protein ◽  
Molecular Mechanisms ◽  
Interaction Analysis ◽  
Super Resolution ◽  
M Protein ◽  
Docking Simulations ◽  
Cytoskeleton Organization ◽  
Rat Brainstem ◽  
Rabies Pathogenesis

Abstract Multifunctional matrix protein (M) of rabies virus (RABV) plays essential roles in the pathogenesis of rabies infection. Identification of M protein interacting partners in target hosts could help to elucidate the biological pathways and molecular mechanisms involved in the pathogenesis of this virus. In this study, two-dimensional Far-western blotting (2D-Far-WB) technique was applied to find possible matrix protein partners in the rat brainstem. Recombinant RABV M was expressed in Pichia pastoris (P. pastoris) and was partially purified. Subsequently, 2D-Far-WB determined six rat brainstem proteins interacted with recombinant M protein which were identified by mass spectrometry. Functional annotation by gene ontology analysis determined these proteins were involved in the regulation of synaptic transmission processes, metabolic process, and cell morphogenesis-cytoskeleton organization. The interaction of viral M protein with selected host proteins in mouse Neuro-2a cells infected with RABV was verified by super-resolution confocal microscopy. Molecular docking simulations also demonstrated the formation of RABV M complexes. However, further confirmation with co-immunoprecipitation (Co-IP), was only successful for M-actin cytoplasmic1 interaction. Totally, our study revealed actin cytoplasmic1 as a binding partner of M protein, which might have important role(s) in rabies pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document