The Insane Zoonotic Trip That is Rabies

Genomics Revolution

Genomics Revolution

Guest Hosts: Giselle Bahena & Diamond Johnson

Episode 49 – Rabies Lyssavirus

Script:

Welcome to Genomics Revolution. This is Giselle Bahena and Diamond Johnson from the 2020 Hiram College Genetics course hosting this episode covering the Rabies lyssavirus. As the scientific name of this virus implies, the disease that results from such infection is commonly known as Rabies. This disease has been around since antiquity and the earliest writings about it was found in 300BC in Mesopotamia.2 It was discovered through the infectious bite from one animal to the other. The biggest red flag that indicated a rabid animal was excessive salivation which then required preventative actions to take place in order to protect against the virus being transmitted elsewhere. It is important to understand the virus as transmission does not only occur between one animal and the other, rather humans are also at risk from such infectious bites as well. Thousands of people in third would countries continue to die of Rabies and if one is not educated nor treated for the disease, its impact on the central nervous system will take place and result in death.

The Rabies virus genome is a single stranded, antisense, non-segmented, negative stranded RNA of approximately 12kb.1. There is a 50 nucleotide leader sequence that is followed by the the five genes in the genome. The proteins encoded by these five genes are nucleoprotein(N), phosphoprotein(P), matrix protein(M), glycoprotein(G) and polymerase(L), all of which make up the structure of the bullet-shaped virion.1 Fusion of the rabies virus envelope to the host cell membrane initiates the infection process and from this point the bullet-shaped virion, with 10nm spike-like glycoprotein peplomers covering its surface, penetrates and enters the host cell cytoplasm via pinocytosis.1 Next, the viral RNA is uncoated and the transcription process of producing messengers RNAs(mRNAs) begins. Since the lyssavirus is a negative single stranded RNA genome, these mRNAs must be transcribed as they are needed to permit virus replication later on in its cycle of infection and replication.1 Now, the synthesized mRNAs are translated into the genomes structural proteins. As G protein glycosylation is processing, the first step in viral replication occurs by synthesizing full length positively stranded copies of the genome that serve as templates for the final synthesis of the negatively stranded genome.1 When this switch to replication occurs, RNA transcription then becomes non-stop as stop codons are ignored. Finally, the assembly process of the bullet-shaped virion takes place and proceeds to its budding formation.

There has been an unrecognized member of the lyssavirus genus found in bats that is similar to the one found in dogs, both of which have been seen to be transmitted in humans.3 This is important because with the genome sequence of the lyssavirus, another member in the family was able to be identified along with other animals who would not be typically associated with caring the such virus. On a similar note, sixty nine rabies virus isolates from various parts of the world were partially sequenced and compared to thirteen representative isolates of the six lyssavirus genotypes in order to analyze their genetic diversity.4 The analysis was performed on each of their complete nucleoprotein coding gene and it was discovered that all of the rabies virus isolated belonged to genotype 1, most likely diverging by the accumulation of synonymous mutations.4 With this being said, having the knowledge that the nucleoprotein is highly conserved among all the isolates is important as it can be used as a potential target for preventing the viral Rabies infection. For example, a complementary RNA can can be created to hybridize with the nucleoprotein mRNA and prevent its translation by targeting it for degradation. This would ultimately prevent one of the key structural proteins of the bullet-shaped virion to be made and prevent the virus from being transmitted. It has also been discovered that the human monoclonal antibody (HuMAbs) may serve as an alternative treatment against less affordable treatments. HuMAbs was found to be the best monoclonal antibody as it neutralized all the rabies viruses it was tested against, it recognized both minor site A and antigenic site III and was able to protect hamsters from the most lethal dose of the virus.5 This is another important finding as even if an individual is infected, HuMAbs can be applied for post-exposure protection against the viral genome.

Thank you for listening to this episode of Genomics Revolution, we hope you enjoyed your time and were able to learn something new from this talk.

References:

1. What is Rabies? Centers for Disease Control and Prevention. 2019 Jun 11 https://www.cdc.gov/rabies/about.html

2. A brief history of rabies: Microbiology. 2017 Apr 12 https://www.labroots.com/trending/microbiology/5761/brief-history-rabies

3. A brief history of rabies: Microbiology. 2017 Apr 12 https://www.labroots.com/trending/microbiology/5761/brief-history-rabies

4. Kissi B, Tordo N, Bourhy H. Genetic Polymorphism in the Rabies Virus Nucleoprotein Gene. Virology. 1995;209(2):526–537.

5. Sloan SE, Hanlon C, Weldon W, Niezgoda M, Blanton J, Self J, Rowley KJ, Mandell RB, Babcock GJ, Thomas WD, et al. Identification and characterization of a human monoclonal antibody that potently neutralizes a broad panel of rabies virus isolates. Vaccine. 2007;25(15):2800–2810.