What is Poxviruses?
Poxviruses are a group of large and complex viruses that contain double-stranded DNA. They reproduce themselves completely within the cells they infect, without needing to use the cell’s nucleus. These viruses are particularly well-known because one of them, the variola virus, was responsible for smallpox – a disease that has caused more human deaths than any other infectious disease.
Out of the 28 types of poxviruses, only four can infect humans: Orthopoxviridae, Parapoxviridae, Yatapoxviridae, and Molluscipoxviridae. Human-specific species are the orthopox virus, variola (smallpox), and molluscum contagiosum (MCV), a virus that specifically infects a type of skin cell known as a human basal keratinocyte.
In terms of their structure, poxviruses are quite large. They have a brick-shaped outer layer made up of proteins and lipids and packed with mature viruses, each one ready to infect a cell. The DNA of the virus is kept within a protein core, surrounded by the machinery it needs to copy itself – including its own special version of an enzyme called DNA-RNA polymerase.
What Causes Poxviruses?
Poxviruses are unique because they don’t need to attach to a specific cellular receptor or protein to infect a host. Instead, they gain access to cells through a complicated multi-step process. This involves using common elements found on the surface of mammalian cells like glycosaminoglycans (GAGs), which are sugars that help cells stick together, or components of the material that holds cells together, known as the extracellular matrix.
At least eleven different proteins are involved in this intricate process. But just getting inside the cell is not enough to ensure the virus can take hold, as it doesn’t have a specific preference for any mammalian cell. What makes a cell a good target for the virus isn’t about having the right surface protein. It depends more on how that cell responds to this unexpected viral invasion.
In a suitable host, the body’s defense mechanisms, including the release of defensive proteins like INF-gamma and the cell’s self-destruction process known as apoptosis, will be put on hold. Ironically, it’s these same defense reactions that trigger the virus to progress its invasion, leading to more detailed virus-building activities like multiple mRNA transcription sequences, assembly, and eventual spread of the virus.
This virus-host interaction is quite a delicate process. It involves a range of cellular activities like controlling the cell growth (mitogen arrest), differentiation (process where a cell changes from one type to another), signaling (communication between cells), and cellular immune system regulation.
Risk Factors and Frequency for Poxviruses
Smallpox is known to be one of the most damaging diseases in history and was recognized in many ancient cultures because of its unique symptoms and rash. As a poxvirus, it was highly resilient and contagious, with an infection rate in people who weren’t vaccinated exceeding 85 percent. It is thought that it mainly spread through droplets in the breath but could also live for years in the scabs of people who were infected and was tough enough to spread by touching infected objects.
Attempts at creating a vaccine were made as early as the fourth century in China and India, using milder forms of the virus. However, it wasn’t until Edward Jenner isolated the cowpox virus in 1786 that a formal vaccine was established. What made this vaccine so powerful was its strong immune response, the fact that there were no non-human places for it to live and breed, and its slow mutation rate, which led to smallpox being officially eradicated in 1980.
Molluscum contagiosum, another poxvirus, often causes skin conditions in children. In adults, genital lesions are usually considered to be sexually transmitted. In people with weakened immune systems, it can cause widespread, disabling skin conditions.
Other poxviruses, like monkeypox and orf virus, can infect humans and can spread from person to person. However, many are largely diseases found in animals, with a low infection rate in humans and isolated occurrences.
Signs and Symptoms of Poxviruses
It’s crucial to thoroughly evaluate each patient, paying particular attention to their vaccination status, any potential exposure to harmful substances, travel history, and occupational risks. Warning signs include if the patient has had contact with the virus for research purposes or been near known sources of animal-based disease transmission, such as bushmeat or hunting activities.
A fully detailed physical examination is also essential. Many poxvirus lesions, particularly those related to molluscum, have a characteristic appearance that can be described as a ‘dome and crater’. Other potential signs of poxvirus infection to look out for include extremely high fever, enlarged lymph nodes, and abnormalities in oral or eye exams, which might indicate the presence of particular complications like pneumonitis.
Testing for Poxviruses
If you suddenly have a high fever followed by a rash with blister-like bumps or pustules that look the same and are all at the same stage of development and your palms or soles are not spared, you could possibly have variola, also known as smallpox. A unique feature of these bumps is that they have a small dimple or depression in the center. If your doctor strongly suspects this, it’s very important that you’re immediately quarantined to a special room with negative pressure to prevent the disease from spreading. Your doctor may also want to vaccinate you and start contact tracing, which means finding and testing everyone who has been in close contact with you. They will also notify health officials.
The first step is to rule out smallpox. To confirm the disease, skin samples can be examined to see if there are specific virus nucleation sites called Guarneri bodies present in the host cell, which is an indicator of a poxvirus infection, but this doesn’t show if it’s specifically smallpox. To specifically identify smallpox, your doctor can use a technique called polymerase chain reaction (PCR). They can also use a viral culture, which is the most reliable test, but it needs to be done in a safety level 4 laboratory, which has strict safety and containment measures for dangerous viruses.
In the case of molluscum contagiosum, which is a common and generally mild skin infection, testing usually isn’t necessary because the distinctive look of the bumps makes it relatively easy for doctors to identify by sight. However, if the bumps appear in the genital area, especially in children, your doctor will probably run tests for sexually transmitted infections (STIs) to be safe.
Treatment Options for Poxviruses
The first vaccines developed were extracted from calf-lymph. Following that, the next wave of vaccines were grown in kidney epithelial cells (Vero cells) harvested from an African green monkey. When administered within three days of being exposed to a disease, these vaccines can drastically reduce or even stop the progression of the disease. If given within a week, they may alter and mitigate the course of the disease.
Tecovirimat is currently the only approved drug for treating infections caused by orthopoxvirus, which includes diseases such as smallpox. It works by blocking the progress of the virus both in lab conditions and in several different animal models. The drug targets a specific protein essential for the virus to spread, and it is well tolerated by patients, with virus-specific effects.
Another possible treatment for diseases caused by poxviruses is a drug called cidofovir, which acts against a virus-specific enzyme involved in its replication. Brincidofovir, a variation of cidofovir that can be taken orally, is also a potential treatment. While these drugs can cause kidney problems, they have been shown to reduce mortality in at least one animal model when administered in increasing doses.
Smallpox, a disease caused by a type of poxvirus, can lead to severe complications such as bleeding, hemodynamic instability, bacterial superinfections in the bloodstream, and shock due to heart failure. Therefore, the doctors will regularly monitor the vital signs, blood counts, and coagulation profiles in patients.
Infections by Molluscum contagiosum, a virus that causes small wart-like bumps on the skin, typically resolve on their own unless the patients have a weakened immune system. Treatment options include topical podophyllotoxin, imiquimod, cryotherapy (treatment using cold), and curettage (scraping off the bumps). Patients are advised to avoid touching the affected areas to prevent spreading the virus to other parts of their body.
What else can Poxviruses be?
Monkeypox is a disease that can often look like smallpox. They both have similar spots and follow similar timelines. However, monkeypox usually includes lymphadenopathy, which is swelling of the lymph nodes. It’s crucial to be careful since monkeypox can spread from person to person, but not as rapidly as smallpox.
In addition to monkeypox and smallpox, severe chickenpox should also be considered. This could be the case especially if the rash, filled with small, fluid-filled blisters, does not affect the palms of the hands and the soles of the feet and if the size and progression of the rash change over time. A secondary syphilis rash also affects the palms and soles, but it won’t change or spread as quickly.
A proper history check should also be able to rule out drug-induced reactions and hypersensitivity rashes like toxic epidermal necrolysis, also known as skin peeling.
What to expect with Poxviruses
Generally, the most common form of smallpox had a fatality rate of about 30 percent. However, younger patients may sometimes develop a severe form of the disease, known as flatpox. This form produced unique skin spots that were soft and velvet-like, differing from the usual blister-like spots in regular smallpox. People suffering from this variant also suffered from harsh early symptoms including sustained high fevers.
Older patients, or those who were pregnant, were more likely to develop a lethal variant called hemorrhagic smallpox. This could lead to sudden and severe loss of platelets (blood cells that help your body form clots to stop bleeding). This could make it look like other bleeding disorders caused by viruses. But, this condition was made worse by factors such as a lower ability for the blood to clot, fluid accumulating in tissues, bleeding, and low blood pressure. The situation got more complicated when liver and bone marrow began to fail, which further worsens the instability of blood flow.
These severe forms of smallpox were usually fatal, resulting in very poor outcomes.
No other human infection caused by poxviruses, the family of viruses to which smallpox belongs, carries such a high risk of death. Other diseases caused by these viruses, such as cowpox and monkeypox, are much less severe, with death rates only rarely exceeding 5 to 10 percent.
Possible Complications When Diagnosed with Poxviruses
Survivors often experience impactful scarring from healed lesions, particularly if the lesions had become superinfected. Problems related to eyes, like inflammation of the cornea (keratitis), corneal ulcers, and even eventual blindness, have been reported. There’s also a unique cause of blindness. Additionally, survivors may face serious respiratory and systemic complications like pneumonia, respiratory failure, a bluish tint in the skin due to lack of oxygen (cyanosis), bacterial infection in the bloodstream (bacteremia), a response to bacteria in the bloodstream that can lead to organ damage (sepsis), and a sudden drop in blood pressure (hemodynamic shock).
Common Complications:
- Debilitating scarring from healed lesions
- Ocular complications such as keratitis and corneal ulceration
- Blindness (including a unique form)
- Pneumonia
- Respiratory failure
- Cyanosis (a bluish tint in the skin due to lack of oxygen)
- Bacteremia (bacterial infection in the bloodstream)
- Sepsis (a response to bacteria in the bloodstream that can lead to organ damage)
- Hemodynamic shock (a sudden drop in blood pressure)
Preventing Poxviruses
Vaccinia and variola, two types of poxviruses, caused major problems in human history. Even though variola is now extinct, other poxviruses still pose a risk to humans. It’s believed that variola prevented other poxviruses from becoming widespread among humans, because it was so prevalent. But now that variola is gone, there’s a chance for other poxviruses to emerge and spread.
In light of the recent COVID-19 pandemic, we need to invest more in understanding how viruses from animals can jump to humans. This includes understanding how harmful these diseases can be, how they spread, and how we can prevent them from spreading. Poxviruses in particular need to be studied more closely. We have seen in the past year that we don’t know enough about these diseases, and this lack of knowledge can have serious consequences.
In the end of the 20th century, people started to worry about the possibility of smallpox being used as a biological weapon. Smallpox is another type of poxvirus, that can be very deadly. This led to the creation of many smallpox vaccines, which are stored and ready to be used if needed. Although the exact number of vaccines available in the U.S. strategic defense stockpile is kept secret, it’s generally believed that there’s enough to vaccinate every person in the U.S.