Rabies in human brain: It can hijack your system!


Rabies is a zoonotic disease, i.e., transmitted from animals to humans. Any animal infected with the virus can transmit it to humans via a bite. If in case the patient’s history doesn’t record any animal bite, it means the spread is via aerosols. The virus cannot enter the host via the skin; the only route of entry is open wounds and mucus membranes. The target of the Rabies virus in human is the central nervous system, i.e., a neurotropic virus.  

The two modes of infection include- hyperactivity (hydrophobia) and numb (paralysis). The glycoprotein of the virus attaches to the acetylcholine receptors, taking over our muscle control, resulting in paralysis.

Signs and symptoms of Rabies in the human body

The incubation period of the virus ranges from less than ten days to more than two years. The average incubation period is usually 1-3 months. However, the incubation period depends on the proximity of an animal bite to the brain. A bite on the leg results in a more extended incubation period, compared to a bite on the neck. The infection progresses through four stages in man- prodrome, acute neurological period, coma, and death.

  • Prodrome: It includes early flu-like symptoms– fever, headache, nausea, sore throat, and cough.
  • Acute neurological period: This stage involves neurological complications– Confusion, hyperventilation, hyper-salivation, hydrophobia, hallucination, nightmares, and insomnia.
  • Coma and death: Once the patient enters a coma, there are high chances he/she will die within a couple of hours unless provided with ventilator support.

The pathway of Rabies to the human brain

Rabies binds to a nerve growth factor and enters the neurons via the peripheral nervous system. It takes control of the transport components of the cell and reaches the spinal cord. In the spinal cord, it takes the first transport molecule to reach the brain. During this period, it damages organs one after the other.

The axonal transport outside the CNS is extremely sensitive, and any disruption can lead to neurological complications like Alzheimer’s. If researchers find the exact mechanism of transport, drug delivery into the nervous system will be made much simpler. Moreover, they can make the medication work effectively.

How Rabies causes hydrophobia?

A person infected with Rabies finds it difficult to swallow water. They start facing discomfort in the neck and throat. This discomfort with a chain of processes results in fear of water. However, the virus has a role to play in this process. Even after infection, if the person is capable of swallowing water and saliva, then lysozyme and other enzymes can harm the virus.

The virus fears water; it tricks our brain into thinking we fear water, eventually developing hydrophobia in one. 

Treatment

Endosomes help in viral transport to neural cells. Hence studies suggest the use of the drug, Emetime. Emetime attacks virally infected endosomes and immobilizes them. They can now only move short distances at a slower speed. This process inhibits viral transport to the brain. Other protein syntheses will not interrupt this process exhibiting the inhibitory control of Emetime. 

However, the best way to avoid infection is by minimizing the exposure to rabid animals. Individuals suspecting an animal bite should seek immediate medical care. An immunoglobulin injection soon after the exposure, attacks the virus and stops its progression through the nerves. Once the symptoms arise, it is challenging to treat the patient.

Besides, a vaccine shot provides immunity for the infection. It is the best method to avoid Rabies before it starts breaking down your nervous system.

Structure of Rabies virus

Rabies virus is a negative sense, non-segmented, single-stranded mRNA. It consists of a protein coat, called nucleocapsid, enclosing the genetic material. The genome is small coding for only five genes– ribonucleoprotein (RNP) complex and the envelope; the transcriptase (L), Nucleoprotein (N), transcriptase-associated protein (NS) comprise the RNP complex.

A lipid bilayer coat encloses the nucleocapsid and consists of the spike proteins. The spike proteins of the virus, the glycoproteins,  act as receptors in the human body, generating an immune response.  

The RNP complex proteins accumulate in the cytoplasm of the infected neural cell. This accumulation serves as a diagnostic purpose for the presence of the virus inside the human body. Whereas, the nucleoprotein plays a vital role in replication and transcription (RNA to proteins). 

On the other hand, the Matrix (M) protein and glycoprotein (G) associate with the lipid envelope. The glycoprotein forms numerous spike proteins, tightly attached to the lipid envelope. The phosphatidylserine acts as a surface receptor. 

Multiplication of the virus

With the help of spikes, it attaches itself to the host neural membrane. After that, via endocytosis, it reaches the cytoplasm and starts uncoating the viral envelope, exposing its genetic material. The viral enzymes aid in the conversion of the negative strand to a positive-strand (capable of synthesizing the viral proteins).

The protein- RNA dependent RNA polymerase– now aids in the replication of the viral genome. The positive-sense RNA acts as a template for the synthesis of negative-sense RNA progeny virions. Viral proteins mediate this process. This process of viral replication is often in muscle cells.

Diagnosis of rabies virus in the human body

The primary step for the diagnosis of Rabies infection is to find whether a rabid animal has bitten the patient. This confirmation makes the diagnosis straightforward. The doctors sometimes fail to suspect the disease due to a lack of a thorough history.

Moreover, rabies infection can mimic various other viral infections responsible for causing encephalitis like Herpes and Zika virus. Poliomyelitis can also be a reason behind paralysis. Guillain-Barre syndrome and different allergic reactions to drugs can mimic the inflammatory response of Rabies. No thorough diagnosis gives negative results. 

Clinical diagnosis

The primary detection method is using viral neutralizing antibodies. Although, if the test remains unconfirmed, saliva and serum analysis is employed, if the person is unvaccinated.

However, the serum analysis is appropriate only during the first 2-3 weeks of infection. Cerebrospinal fluid analysis is a confirmed diagnosis. Since the virus appears late in CSF, it is useless if performed after serum analysis.

One of the most efficient methods includes direct immunofluorescence testing on a skin biopsy. However, it is a sensitive method and requires fresh tissue. If fresh tissue is unavailable, enzyme digestion of the available tissue can enhance the results. 

Related: Zika virus: the reason behind microcephalic fetuses

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