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Varicella zoster virus is one of the herpesviruses and it causes two diseases - varicella or
chickenpox, and herpes zoster also known as shingles.
Zoster actually refers to a type of belt used by ancient Greek warriors because of the belt
like appearance of shingles.
Now, let’s first talk a bit about the nervous system - it consists of two parts.
The central nervous system which includes the brain and the spinal cord, and the peripheral
nervous system includes the nerves that fan out from the central nervous system to reach
the skin, muscles, and organs.
Peripheral nerves that originate from the brain are called cranial nerves, and they’re
in charge of motor and sensory innervation of the head and neck.
A specific cranial nerve, cranial nerve V, is the trigeminal nerve and it’s responsible
for the sensation in the face.
Its sensory neurons create a nerve cell cluster called trigeminal ganglion, located in the
bones on the side of the face between the eyes and ears.
The peripheral nerves originating from the spinal cord are called the spinal nerves.
Each nerve is formed by a dorsal and a ventral root.
Ventral roots contains neurons that carry motor innervation from the spinal cord to
the muscles.
Sensory information, like touch, temperature, pain, and pressure from the skin and other
tissues travel through 1st order sensory neurons, in the dorsal root ganglion near the spinal
cord, then through the dorsal root, and into the spinal cord, where it synapses with the
2nd order neurons.
Now, each spinal nerve is in charge of the sensation of a specific area of the skin,
called a dermatome.
For example, if you step on a lego, the pain would be carried by the S1 nerve, but if you
hit your big toe on a table leg, the pain would be carried by the L5 nerve.
Varicella zoster virus is a double-stranded DNA virus, protected by a protein coat called
capsid, which is enveloped in a lipid membrane.
The virus initially enters respiratory epithelial cells - but eventually spreads to numerous
cell types.
It gets into all of these cells by fusing its membrane with the cell membrane and releasing
the capsid inside the cell.
The capsid binds to the nucleus and injects it with viral DNA, where it’s copied.
The viral genes are transcribed into RNA and go over to the ribosomes, where they are translated
into capsid proteins.
The capsid and viral DNA fuse together.
They go through the Golgi complex, a cell organelle in charge of packing proteins, to
get their lipid membrane and finally the newly formed viruses leave the cell.
Leaving behind a dead cell.
When an infected person sneezes or coughs, the viruses leaves the lungs and get released
into the air.
The virus can also be transmitted through contact with the oral or skin lesions of the
infected person.
When the virus comes in contact with the respiratory mucosa or the skin of a new person, it starts
replicating in the epithelial cells.
It soon gets picked up by nearby immune cells and gets transported to a nearby lymph node.
The virus now causes primary infection called varicella or chickenpox, and it has two stages
- primary viremia and secondary viremia.
In primary viremia the virus infects a part of immune system in the liver and spleen called
the reticuloendothelial system, which is made of phagocytic cells.
About two weeks after entering the body, the virus starts infecting immune cells themselves
- specifically T cells - and that is considered the secondary viremia.
Infected T cells start expressing proteins that bind to receptors on the skin cells.
It’s a bit like the virus is hitching a ride in the T cell to get to the skin.
Once the T cells reach the skin, they release the viruses, which start infecting keratinocytes.
The infection spreads through the skin, going directly from cell to cell.
Sometimes the infected keratinocytes start to fuse together and create giant multinucleated
cells called Tzanck cells.
Uninfected cells start secreting interferons alpha and beta, which inhibits viral protein
synthesis and protects those cells from getting infected.
As a result, we get tiny lesions on the skin separated by normal areas of skin.
In addition to infecting keratinocytes, the virus also infects sensory neurons in the
skin, and in those neurons it travels retrogradely, meaning backward through the neuron to the
dorsal root ganglia or if it’s on the face, the trigeminal ganglion.
Over time, when the adaptive immune reaction kicks in, most of the viruses in the body
are eliminated, but the ones in the ganglions are spared and can remain dormant for many
years.
Most commonly, the virus establishes a latent state within the trigeminal ganglia and the
dorsal ganglia.
Later on, if the immune system weakens, due to aging, stress, or immunosuppressive therapy,
the virus can be reactivated.
It can then travel back up through the sensory nerve, anterogradely to the skin and cause
an infection in the innervated dermatome - that’s called herpes zoster or shingles.
With both chickenpox and shingles, the most common complication is a secondary bacterial
infection of the skin lesions.
So, if the liver becomes infected, hepatitis can occur.
If the virus spreads to the lungs we get pneumonia.
If the brain or its protective membrane, called the meninges, become inflamed, encephalomeningitis
could occur.
Symptoms of chickenpox begin about 2 weeks after it enters the body.
The infection usually causes a fever, headache and overall weakness.
After a couple days, skin lesions start to appear on the scalp, face, and trunk.
At first, there are flat, red, itchy spots called macules.
Over time, they become elevated and develop into papules, and then into small fluid-filled
vesicles.
Within 1 to 2 days the vesicles begin to crust over and form scabs.
After about 5 days the scabs fall off, usually without leaving a scar.
New crops of lesions are continuously forming in different places on the body every 3 to
5 days, so it’s possible to see lesions in different phases at the same time.
In addition to the itchy lesions, painful sores can appear on mucosal surfaces like
inside the mouth.
In shingles there’s typically pain, itching, or tingling in the area where the rash will
develop.
The rash itself is usually in a single stripe of vesicles around either the left or the
right side of the body or on one side of the face.
It usually takes 4 weeks for the rash to disappear, but there can be pain in the affected dermatome
which lasts for more than 90 days called postherpetic neuralgia.
Chickenpox and shingles are usually diagnosed based on the way that the skin lesions appear,
but the diagnosis can be confirmed by using the Tzanck test to look for multinucleated
giant cells in the fluid of the vesicles.
More commonly, blood test for varicella zoster antibodies or PCR can be done to look for
viral DNA.
Chickenpox treatment mainly includes the use of topical antipruritic medications to help
reduce the itching.
Also, analgesics and anti-inflammatory medications can help reduce the fever, but aspirin shouldn’t
be used in someone with chickenpox, because it can trigger Reye syndrome.
In Reye syndrome, the liver gets affected by both varicella zoster virus and aspirin
and it leads to a buildup of ammonia in the body.
In immunocompromised individuals, antivirals like acyclovir, famciclovir, and valacyclovir
can be used.
In some situations, varicella-zoster immune globulin or VZIG which are anti-varicella
antibodies can be given to treat immunocompromised or pregnant individuals.
Finally, varicella vaccine can be used to prevent chickenpox by helping the body mount
protective immunity against a weakened form of the virus.
Similarly, zoster vaccine can be used to reduce zoster - which is more common in adults.
All right, as a quick recap varicella zoster virus is a herpesviruses that causes primary
infection in the lymph nodes and secondary infection in the keratinocytes and neurons
in the skin.
From the neurons in the skin, it travels retrogradely to the nerve ganglia, where it remains dormant.
Chickenpox is characterized by a rash on the scalp, face, and trunk that contains macules,
papules, vesicles and scabs at the same time.
Herpes zoster or shingles is caused by the reactivation of the virus, with vesicles located
along one dermatome.
Treatment is usually symptomatic, and in some cases includes antiviral drugs.