Lyssavirus

Lyssavirus

Contents

Introduction

Pathophysiology

Symptoms

Immune responses

Vaccines

Introduction

Lyssavirus is a genus of RNA that can cause the disease rabies that affects warm blooded mammals. Rabies is classified as a Encephalitic disease [diseases that causes inflammation of the brain cause by an infection] and is widely regarded as the deadliest disease in the world. The disease is spread through saliva or bodily fluids and are mostly transmitted via bites by animals such as stray dogs or cats. Other types could include scratches or small chances through organ transplants.

Lyssavirus (Genus) is composed of 17 known viral species and one putative [genes who’s functions are unknown] All species of this virus are bullet shaped and contain a negative sense RNA genome of approximately 11000 nucleotides [Viruses that use the genome as template for the synthesis of all mRNAs]

The main proteins coded by the genome are

Nucleoprotein – proteins that have a relationship with the genetic material

Phosphoprotein – any protein group donating a chemically bound phosphoric acid

Matrix protein -

Glycoprotein - proteins that form layers on the inside of the viral envelope

Polymerase containing a transcriptional bias – a polymerase that is involved in transcription of viral RNA

The most common type species is the RABV which causes the most significant impact and is mostly spread through dogs.

Pathophysiology

Viral entry of the Lyssavirus is most common on through bites of stray dogs via saliva into the tissues. After infection the RABV virus typically infects the muscle cells. This process occurs with the nicotinic acetylcholine receptor [ion channels found on the skeletal neuromuscular junction and acts as transmissions and receptors found throughout the nervous system] during this time frame the virus replicates

Virus replication

The viral G glycoprotein will attach to the receptors on the host cell

A process called Clathrin mediated endocytosis occurs

[the major endocytic pathway in mammal cells]

[endocytosis is the way that external material enters the cell]

The virus membrane then fuses with the cell membrane and releases ribonucleocapsids into the cytoplasm

Transcription then occurs

The virus will begin to replicate when enough nucleoproteins are present

The virus will then bud through the ESCRET complexes which are transport cages

The virus will remain in the infection region for periods of time which links to the characteristics of the disease when they stay undetected for periods of time presenting no noticeable symptoms.

The virus could also infect motor endplates which gives them full entry to the nervous system and the main target the brain.

The virus travels through the PNS [The peripheral nervous system : The nervous system outside of the brain and spinal cord] and it travels towards the central nervous system. The virus is moved from neurons to neurons and contaminates and replicates the neurons. The virus travels through a receptor p75NTR which is non essential in the process but increases the rate. Proteins found will help the virus travel by manipulating different structures and help with more efficient viral transcription and replication.

When the virus reaches the CNS it continues to spread by both zonal and trans-synaptic transport and it continues to spread by metabotropic glutamate receptors which is a receptor found throughout the CNS. When the virus enters the brain is proliferate [divides rapidly] and causes symptoms to finally appear. It will also spread to the saliva glands where it will contaminate and become a vessels for infections.

Symptoms

There is a range of symptoms that are unexplainable. The most common symptoms include twitching and jerking. Rabies that are infected with stray dogs have a classical symptom of hydrophobia [fear of water] and acrophobia [fear of flying] symptoms will also occur around the local area of the wound. These symptoms are mainly linked to rabies while symptoms such as common colds and coughing are linked to a wider range of encephalitic diseases. Some serious symptoms can also occur such as paralysis, coma or death caused by organ failures. Another symptom present in most cases are muscle weakness due to how the virus infects muscle cells. Rarer symptoms include mitochondrial deficiency. As the lyssavirus mainly targets the nervous system and the brain, there is a high chance for neurological dysfunction and losing the ability of speech or the maintain composure. There are are different survival times of different rabies species but all have a high chance of fatality of not treated or vaccinated.

Immune response

Once the body is infected an immune response is triggered. At the beginning it is though to be affected but as the virus replicates and poorly stimulate the activation and maturation of dendritic cells [immune cell found in tissues also a type of antigen presenting cell] which lowers the effectiveness of antibodies by disrupting the signalling inhibited by a protein. One of the features of the lyssavirus is its ability to remain low and evade immune response. The viruses are multifunctional allowing it the enter replicate and spread and causes it to be undetectable. The proteins contained in the virus can cause immune suppression and inhibits the production of different antivirals. The virus also inhibites the production of interferons which are particles that make the cell transparent. This leads to immune cells unable to recognise infected cells. As soon as the virus reaches the PNS and neurons it is almost unstoppable due to the destructive power of the antibodies and the weak composition for neurons. As the neurons are Important for transmitting chemical signals it is risky to destroy the nervous system to fight the virus. The nervous system has the ability to induce apoptosis of different cells. So as soon as the lyssavirus reaches the nervous system the immune response will be rendered useless. This is why vaccines and treatments are urged to be delivered at early stages or right after an animal bite.

Vaccines

For this section the example will be ABLV also know as Australian bat lyssavirus infection

The vaccine given for ABLV is also given to other species of rabies due to it being from the same family. The vaccine will be given before the exposure (PrEP) while it can also be given after exposure. For post exposure vaccines it is recommended to be given in a week period of exposure as the virus could already move into your nervous system. As explained in the previous section the nervous system is very fragile and could order immune cells to undergo apoptosis or programmed cell death