Description of Varicella-Zoster Virus
Varicella-zoster is a viral infection that causes chickenpox and shingles in humans. The virus is contagious and often results in severe illness in individuals affected (1). It is the known cause of chickenpox in children and adults who have never been infected with the virus (9). On the other hand, in the rare case of reinfection, an individual may experience shingles.
The emergence of shingles is not ordinary because once an individual is affected by the virus, their bodies respond by developing antibodies. The antibodies are formed to help the body fight the virus (2). The virus usually remains dormant in the human body after the initial infection. However, when it is reactivated, it results in shingles disease. The antibodies developed by the body often protect people from reinfection, making the virus lie dormant for a longer duration.
Reinfection by the virus is exacerbated by several factors within the human body. One of the factors that may contribute to the re-emergence of the virus is the inability of an individual’s immune system to clear the virus from the body completely. Additionally, an individual’s age also plays a crucial role in the risk of reinfection by the disease. As people age, their immunity decreases, making them more susceptible to the virus (8). Chickenpox and shingles are distinct diseases with different symptoms caused by the same virus. Therefore, it is essential for individuals affected by the virus to seek medical help from the hospital.
General Characteristics of the Disease
The virus belongs to the herpesvirus family, which includes herpes simplex virus and Epstein-Barr virus. Varicella-zoster is an enveloped virus with a double-stranded DNA genome (3). It replicates in the nuclei of the infected cells to cause the infection. In the laboratory, varicella-zoster is cultured or grown in human embryonic lung fibroblast cells (4).
The virus specimens for clinical sampling are obtained from nasopharyngeal swabs or vascular fluids. The sample obtained through these procedures is then inoculated onto the embryonic lung fibroblast cell culture. The cell is then observed under the microscope to determine how the virus infects it. The varicella-zoster virus causes characteristic cytopathic effects on the cell, which can be observed through the microscope. The cultured virus is then harvested from the infected cells and utilized for different studies.
There are several techniques that microbiologist utilizes to study the varicella-zoster virus. One of the techniques used is the polymerase chain reaction, commonly known as the PCR test. The PCR test is used to study the virus and detect it in clinical samples. The method is used to detect the presence of the virus or viral DNA in a sample of blood, cerebrospinal fluid, or other body fluids suspected of containing Varicella-zoster proteins (5).
The other technique the microbiologist uses to study the virus is serological assays. This technique is applied to help detect antibodies against the virus in blood samples. It is also applied in detecting the same antibodies in animal models, which are used to study the pathogenesis of the disease.
The serological assay or test can be performed using the Western blot technique or the ELISA method. The Western blot method is primarily used to detect the presence of antibodies that bind to a specific protein of the varicella-zoster virus. On the other hand, the ELISA method is used to detect the presence of antibodies that bind to varicella proteins (2). These tests are performed based on the patient’s symptoms and the stage of the infection.
Reservoirs
Varicella-zoster is among the many human-specific viruses that cause viral infections. It exclusively survives in the human body; in other words, it is a human-specific virus (1). The virus, varicella-zoster, can only infect and survive in human cells and is not found in the environment, food, water, soils, air, or other animal hosts. Once in the human body, it evolves to infect and replicates only in human cells.
The viruses from the family Herpesviridae, to which the shingles virus belongs, are known for their characteristic of being host-specific. The virus is host-specific due to its unique interaction with the host cells. The virus requires specific cellular receptors, which are only available in human cells, to penetrate and infect the cells. It has also evolved to evade the human immune response, which is primarily responsible for attacking and eliminating foreign materials, such as viruses, from the human body.
There are no known animal or insect vectors for the varicella virus. This virus cannot survive for an extended period outside the human body. Therefore, humans are the primary host of the virus, and it is not found in any other organism or environmental source.
Diseases Caused by Varicella-Zoster Virus
The varicella-zoster virus causes two distinct diseases: varicella (also known as chickenpox) and herpes zoster (also known as shingles). These diseases are considered mild, but they can become severe if they occur in individuals with compromised immune systems. Before the invention of the chickenpox vaccine, it was estimated that about 4 million Americans contracted the disease in the United States each year (8). This infection resulted in the hospitalization of about 10,500 people and 100 deaths annually (8).
The effects of the virus on the population have been severe, especially before the introduction of the vaccine against the virus in the United States in 1995. The vaccine played a crucial role in reducing cases of chickenpox. It also significantly reduced the number of hospitalizations and deaths due to the diseases caused by the virus.
The vaccine has also played a critical role in reducing the re-emergence of the virus in vaccinated individuals, thereby preventing the development of shingles disease. The vaccine achieves this by stimulating the immune system of vaccinated individuals to maintain immunity against the virus. According to the Centers for Disease Control and Prevention, it is currently estimated that 1 to 4 percent of Americans diagnosed with herpes zoster are hospitalized due to complications related to the disease (8).
Shingles currently causes fewer deaths, with an estimated annual number of fewer than 100 (8). Despite this intervention against the virus, it remains a significant challenge, especially for older individuals and those with compromised immune systems. The most common complication associated with shingles is Postherpetic Neuralgia (PHN). This occurs 90 days after the onset of the rash and can last for weeks, months, and rarely years (8). About 10 to 18 percent of Americans who contract shingles are estimated to develop PHN (8). According to the Centers for Disease Control and Prevention, approximately 1 in 3 people in the United States will develop herpes zoster in their lifetime.
Transmissions
The virus, varicella-zoster, is human-specific and transmitted from person to person. The virus is carried in respiratory secretions and is transmitted when an infected person coughs or sneezes. The virus can be released into the environment through these mechanisms into the air. The droplets are therefore inhaled by others, resulting in infection due to the presence of the virus in the surroundings. Additionally, the virus can be transmitted when an individual comes into contact with the fluids from the rash of an infected person, particularly when the virus is in the blistering stage (1).
This virus is highly contagious, thus it can be passed to people through casual contact. This can easily occur in crowded environments, such as schools, households, and childcare centers, among other settings. The virus enters the human body through the skin, respiratory tract, or mucous membranes and can enter the body through the eyes. Once this virus enters the human body, it infects cells within the respiratory tract or skin. It then replicates and causes disease in the host body.
Symptoms of the Disease
Shingles often begins with pain, itching, or tingling in specific areas of the skin. It is always located on one side of the body, and after a few days, a rash develops. The rash that always forms consists of small blisters (5). The rash caused by the virus can be excruciating, but in other cases, the pain can persist even after the rash has subsided. This condition, known as Postherpetic Neuralgia, occurs after the rash has subsided.
In addition, the disease exhibits some less commonly observed symptoms in addition to these commonly identified symptoms. For example, some patients with shingles experience headaches that can be severe. Another less observed symptom of the disease is low-grade fever. Some patients experience this low-grade fever during the second chickenpox outbreak in their bodies.
People also experience fatigue, a common symptom of many viral infections, including shingles. In addition to fatigue and other symptoms, some patients may experience nausea and vomiting while struggling with shingles. Light sensitivity is a less common symptom in patients with shingles, but some individuals experience light sensitivity in the affected area.
The disease is also associated with joint pain, which primarily affects the area where the rash occurs. In some rare cases, it can also affect the eye, causing symptoms such as redness, swelling, and pain. The long-term effect of the disease often includes Postherpetic Neuralgia, and in rare cases, it can cause loss of vision and other neurological complications.
The symptoms of herpes zoster relate to how the disease enters the human body and how it exits the host’s body. The virus employs multiple routes to enter the human body. First, it can enter the body through the eyes, respiratory tract, or mucous membranes.
Once in the body, the virus then spreads into the skin, where it produces its traits and, therefore, can be identified as shingles or chickenpox. After spreading on the skin, it can be shed from the skin lesions and the respiratory tract. The shedding process can continue even after the rash has disappeared. This allows the virus to exit the body and spread to other people who come into contact with the person.
Virulence Factors
Virulence factors are the molecules that pathogens synthesize and encode in their genome. It is defined as the factor used to determine the ability of viruses, bacteria, or, generally, pathogens to infect and damage the tissues of their hosts. The varicella-zoster virus possesses several virulence factors that significantly contribute to its ability to infect and damage human tissues.
One of the significant virulence factors of the virus is its ability to create latent infections in the nerve cells. For example, after one has been infected with the virus and suffered from chickenpox, the virus can persist in nerve cells in a dormant or latent state (5). When this latent or dormant virus reactivates, it results in the onset of shingles disease. Scientists believe that the virus’s ability to create and maintain latency is a result of the partial expression of latency-associated transcripts (LATs), which have been shown to inhibit programmed cell death, also known as apoptosis, in infected cells.
Another virulence factor associated with the virus is its ability to evade the host’s immune response. The virus employs several methods to evade immune detection.
One of the mechanisms it utilizes to evade immune detection is the downregulation of an important histocompatibility complex class 1 molecule. These molecules are vital for antigen presentation in the T-cells. They are also crucial for the expression of immune evasion proteins, such as the VZV glycoprotein and the immediate-early protein 62, which inhibits the host’s interferon response. The virus also comprises numerous proteins that facilitate its attachment and entry into the host cell. For example, the virus is believed to use the viral glycoproteins (gH/gL) to attach itself to host cells, while depending on the viral glycoprotein (gB) for membrane fusion and entry into the host cell (6).
The virus’s ability to damage the host cells is also possible because it produces various proteins. For instance, the viral immediate-early protein 63 (IE63) has been shown to induce apoptosis in infected cells. In addition, the virus also produces viral early immediate protein 4(IE4), which has been investigated and shown to be responsible for stimulating the production of inflammatory cytokines.
Treatment
The varicella-zoster virus often causes self-limiting diseases, such as chickenpox. Self-limited diseases often resolve on their own after a few weeks. Treatment of diseases caused by the virus often focuses on relieving symptoms of pain and discomfort. The doctor may prescribe antipyretic drugs, also known as fever reducers, to alleviate fever and analgesic drugs, also referred to as pain relievers, to manage discomfort.
In some cases, where complications or severe conditions are present, physicians may prescribe antiviral drugs such as Acyclovir, Valacyclovir, or Famciclovir to prevent the development of complications in patients deemed at risk of complications (7). This often happens to individuals who are immunocompromised and pregnant women. Antiviral medications are also used to shorten the duration and severity of shingles and prevent complications that can lead to Postherpetic Neuralgia.
Other treatment options to help manage the infection and reduce the risk of complications may include bed rest. The doctor may also advise the patient to drink plenty of fluids. This helps them avoid dehydration, a potential complication of the disease.
The doctor can also prescribe creams such as calamine lotion (9). This product has properties that may help patients recover from itching caused by rashes. Nutrition also plays a vital role in recovery from the infection caused by the virus. Patients may be advised to avoid foods high in salt, citrus, and crunchy textures, as well as spicy foods. These foods are believed to irritate oral lesions (9).
Additionally, the virus is likely to cause complications, such as gastritis, in individuals with weakened immune systems. This condition results in stomach inflammation, accompanied by symptoms such as pain, nausea, and vomiting. In such a situation, the healthcare provider may recommend a mild diet to help maintain and ensure the patient’s body is hydrated and nourished while fighting the disease.
The treatment of this viral infection often depends on the stage of the disease. Early treatment is more effective than late treatment. Antiviral drugs are most effective when administered within 72 hours of symptom onset (7). Patients suffering from severe cases, such as Postherpetic Neuralgia, can rely upon gabapentin and pregabalin for pain management, as there is no specific drug or vaccine.
Ongoing medical research is aimed at developing new treatments for VZV infections. This new development includes finding new antiviral drugs for the disease and exploring novel treatment methods, such as immune-based approaches. However, these new approaches are still under investigation to determine their safety and efficacy in treating humans.
Epidemiology
The risk factors associated with the virus include anyone who has had an infection or has been vaccinated against the virus, and is at risk of contracting the infection. Vaccination reduces the risk of contracting herpes zoster. According to the CDC, children who got the vaccine have a lower risk compared to children who were infected with VZV.
In the same study, CDC indicates that about 99.5 percent of people born before 1980 in the United States contracted the diseases associated with VZV (8). This indicates that almost all the adults in the country are at high risk for herpes zoster. The reason for the reactivation of the virus after dormancy is still poorly understood. Another risk factor is having a compromised immune system.
An individual’s weakened immune system can result from diseases like HIV/AIDS, cancer, especially leukemia, and lymphoma, using immunosuppressive drugs, bone marrow, or solid organ transplant, and being pregnant. Children born to mothers who develop the disease in the early phases of their pregnancies are also at a high risk of contracting the virus (8). Apart from the immunocompromised individuals, people who also reside in close quarters, such as in the military barracks, schools, and universities, may also be at an increased risk of the outbreak of chickenpox and shingles.
The outbreak of the disease often follows a seasonal pattern, with the highest incidences typically occurring during winter, at the end of spring, and in areas with temperate climatic conditions (9). The reason for the seasonal incidence of the infection is also not fully understood. However, it is suspected that this may be due to changes in people’s social behaviors or alterations in the immune system during the winter months. The disease, for instance, chickenpox, can occur intermittently or on a large scale. The incidence of the disease also varies, and it relies on factors such as vaccination rates and the availability of people within the society who are vulnerable to the outbreak.
References
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- Sadaoka T, Depledge D P, Rajbhandari L, Breuer J, Venkatesan A, Cohen JI. 2022. A variant allele in varicella-zoster virus glycoprotein B selected during production of the varicella vaccine contributes to its attenuation. mBio 4:e01864-22.
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- Shiraki K, Takemoto M, Daikoku T. 2021. Emergence of varicella-zoster virus resistance to acyclovir: epidemiology, prevention, and treatment. Expert review of anti-infective therapy.
- Center for Disease Control and Prevention. 2023. Chickenpox vaccine saves lives infographic, Centers for Disease Control and Prevention. Web.
- Better Health Channel. 2023. Chickenpox. Web.