What is Human T-Cell Lymphotropic Virus?
Human T-lymphotropic viruses, or HTLV, are a group of viruses that can lead to cancer. These viruses are also known to cause diseases where the immune system is weakened or inflammation occurs. Of this group, HTLV-1 takes center stage. It was the first virus ever shown to be able to cause cancer in humans, and now it’s widely accepted as one of the biggest cancer-causing agents in humans.
In a somewhat fortunate twist, about 95% of people who get infected with HTLV-1 will not show any signs of illness. However, the other 5% may develop dangerous conditions that could be cancerous, cause inflammation, or render them susceptible to other illnesses that take advantage of a weakened immune system.
What Causes Human T-Cell Lymphotropic Virus?
The Human T-lymphotropic virus-1 (HTLV-1) is a type of virus that’s surrounded by an outer wall, with a single strand of RNA inside. Like other members of the Retroviridae family, this virus contains several genes, including an extra one that allows it to produce special control proteins. One of these control proteins, known as Tax, is thought to play a key role in how HTLV-1 affects the human body.
HTLV-1 mainly spreads by infecting a type of white blood cell called lymphocytes – with dendritic cells also prone to infection from free viral particles. What’s unique is that, once infected, these lymphocytes start to produce a chemical that attracts other lymphocytes, creating a “virological synapse.” This process helps to spread the virus more efficiently within specific lymphocytes. Interestingly, HTLV-1 transmission differs from another well-known virus – the human immunodeficiency virus (HIV). Whereas HIV results in high viral loads, HTLV-1 distribution within the body is less intense.
Another notable feature of HTLV-1 is its high genetic stability, which is maintained by its method of replication. After the virus enters a cell, its RNA is converted into DNA and incorporated into the host’s genetic material. The virus can then replicate either by constructing new intracellular particles or through cell division. Its replication process is tightly linked to the host cell’s reproduction, resulting in lower replication rates but very accurate copying. Unlike HIV, HTLV-1 produces a stable genetic product that is less prone to immune evasion.
HTLV-1 is also able to control its own gene expression, which contributes to its ability to evade the host’s immune system. The two key regulatory proteins involved in this process are Tax, which promotes gene expression, and Rex, which suppresses it. This virus integrates itself into the host cell and encourages cell growth and extended survival, thereby protecting itself. Unlike HIV, HTLV-1 infection does not cause cell death; instead, lymphocytes manage to avoid cell death and can transform further.
Risk Factors and Frequency for Human T-Cell Lymphotropic Virus
The Human T-lymphotropic virus-1 (HTLV-1) is estimated to affect between 10 to 20 million people worldwide. This number is hard to determine for sure due to varying testing methods. The virus is common across the globe, but an increase in cases has been noted among people who use drugs intravenously, specifically in the United States. Japan has the highest number of HTLV-1 cases and experiences more adult T-cell lymphoma/leukemia (ATLL) cases than anywhere else. Men are more likely to have ATLL, while more women experience myelopathy/tropical spastic paraparesis (HAM/TSP).
- The most common way HTLV-1 is transmitted is from mother to child through breastfeeding.
- Children who are breastfed have a four-fold higher risk of infection compared to those who are bottle-fed.
- Longer breastfeeding durations increase the risk of transmission, however, babies gain some protection from maternal antibodies during pregnancy.
- Bottle-fed children also face a risk, albeit lower, with a 0.6% risk at one year and 4.6% risk at four years.
Transmission of HTLV-1 sexually occurs predominantly from men to women at a 5:1 ratio. Risk factors for developing HAM/TSP include early age at first sexual encounter and having more than five sexual partners. ATLL is linked more to transmission from mother to child.
The transmission of infected blood carries a high-risk of quick infection. This risk is reduced in places that screen for HTLV-1, such as the US, Canada, UK, Australia, New Zealand, and Brazil. However, a small study suggests recipients of organs from infected donors face a high risk of infection, with 7 out of 10 subjects getting the virus within 4.5 years, and 4 getting HAM/TSP.
While it’s uncertain how much risk healthcare workers face from getting pricked with needles used on infected patients, it’s generally not considered a major concern, and there’s no approved treatment after exposure.
Signs and Symptoms of Human T-Cell Lymphotropic Virus
Acute infections of human T-lymphotropic virus-1 (HTLV-1) often go unnoticed as they usually don’t cause any symptoms. If you’ve recently had a blood transfusion or are a breastfeeding infant with a mother from an area where the virus is common, you may be more likely to be tested. There is no specific treatment for an acute HTLV-1 infection, but it’s important to focus on healthy behaviours, such as safe sex and breastfeeding only when safe, and to keep an eye out for any new symptoms.
ATLL is a form of blood cancer caused by HTLV-1. About 4% of people infected with the virus will develop ATLL, often decades after their initial infection. Signs you may have ATLL include swollen glands, skin rashes, enlarged liver or spleen, and signs of a weakened immune system like infections that keep coming back. You may also have high levels of calcium in your blood, which can damage organs and cause psychiatric problems, and you might have high levels of bone turnover leading to soft spots or holes in the bones.
ATLL progresses differently in different people, and doctors categorize it into four types:
- Acute: This is the most common type and usually has the worst outlook. Symptoms include skin rashes, bone pain, and lung symptoms. Some people may also have opportunistic infections.
- Lymphomatous: This type includes severe swelling of the lymph nodes and spleen without the cancerous cells spreading to other parts of the body. There may also be skin rashes and high calcium levels leading to kidney damage and mental confusion.
- Chronic: This type progresses more slowly than the other types and accounts for about 20% of cases.
- Smoldering: This is the rarest form, with mostly mild skin symptoms and no respiratory or gastrointestinal problems. It affects fewer cells and progresses more slowly.
Another disease impacted by HTLV-1 is HAM/TSP, which damages nerve cells in the spine. This can lead to slow and progressive muscle weakness, and it can also lead to disrupted sensation like vibrations in the limbs, back pain, and bladder problems. In most cases, mental abilities remain unaffected. The severity and speed of disease progression in HAM/TSP vary greatly from one person to another.
HTLV-1 can also cause a variety of other medical conditions, including: meningitis, encephalitis, amyotrophic lateral sclerosis, and conus medullaris syndrome.
- Skin: HTLV-1 can cause a skin infection primarily in children that leads to an itchy rash.
- Eyes: The virus can cause uveitis, inflammation inside the eye, resulting in vision problems.
- Rheumatologic: HTLV-1 has been linked with increased rates of autoimmune diseases like polymyositis, Sjögren syndrome, and Raynaud disease.
- Lungs: The virus is significantly more common among people with bronchiolar diseases like bronchiectasis, a condition that causes persistent coughing and shortness of breath.
Testing for Human T-Cell Lymphotropic Virus
For HTLV-1, a type of viral infection, several lab tests are usually involved in making a diagnosis. Initially, a test called the enzyme-linked immunosorbent assay (ELISA) is used for screening. This test helps detect the antibodies produced in response to the HTLV-1 virus. If the ELISA test comes back positive, a Western Blot test is conducted to confirm the diagnosis. The Western Blot test essentially verifies the presence of antibodies against specific proteins of HTLV-1. The polymerase chain reaction (PCR) test is also beneficial as it can determine the amount of virus present and can differentiate between HTLV-1 and HTLV-2.
ATLL is a kind of cancer that affects white blood cells. When diagnosing ATLL, doctors usually find a significantly increased white blood cell count. Analyzing blood and bone marrow cells is necessary for diagnosis and classification of ATLL. The unique appearance of diseased white blood cells, sometimes referred to as “flower cells,” is one of the key findings.
Other than blood tests, a biopsy of the lymph nodes, skin, or other tissues may be needed, especially if doctors suspect that lymphoma, a type of cancer affecting lymph nodes, is present. On the other hand, several markers, like serum CD25, thymidine kinase, and neuron-specific enolase, can predict the disease progression, but these tests are usually conducted at specialist centers.
HAM/TSP is a disease caused by the HTLV-1 virus that affects the nervous system. The World Health Organisation has defined a set of criteria for its diagnosis that includes clinical findings, imaging, and lab tests. However, often in clinical practice, doctors also employ new techniques like PCR to measure the HTLV-1 viral load in the cerebrospinal fluid (CSF), which surrounds the brain and spinal cord. Magnetic resonance imaging (MRI) of the nervous system might point out specific changes in the brain’s white matter or shrinking of the spinal cord. Typical findings in CSF include a slightly increased count of white blood cells, moderately increased protein levels, and detectable antibodies against the HTLV-1 virus.
It’s worth noting that sometimes there can be confusion when naming different human T cell viruses. For instance, the virus called HTLV-3 is now referred to as the Human Immunodeficiency Virus (HIV). And HTLV-4 was once synonymous with HIV-2. This confusion sometimes leads to diagnostic mistakes where most test requests meant for diagnosing HTLV ended up being intended for HIV diagnosis.
Treatment Options for Human T-Cell Lymphotropic Virus
For HTLV (a type of virus), no vaccine exists at the moment. Researchers believe that certain features of the virus, such as its low variability and the ability of humans to develop immunity against it, make it possible to create a vaccine. Some animal studies have even resulted in promising outcomes. Researchers have also identified the CCR4 receptor as a potential target for therapy because it plays a significant role in spreading the virus and the body’s reaction to it.
In terms of treatment for ATLL (a type of cancer caused by the HTLV virus), various methods have been compared to try and find the best approach for patients. One approach uses a combination of medications in an antiretroviral therapy, which seems to be helpful for lymphomatous ATLL, a specific type of the disease. Multi-agent chemotherapy, a treatment which uses multiple drugs to kill cancer cells, appears to work better for acute aggressive leukemic ATL, another form of the disease. If a patient doesn’t respond to one type of treatment, doctors typically switch to the other.
For younger patients with aggressive disease, intense chemotherapy followed by a transplant of stem cells from a healthy donor (allogenic hematopoietic stem-cell transplantation) has shown promise. However, since the average age when patients are diagnosed is 68, many are seen as too old for this treatment. For older patients, a long-term course of chemotherapy with several drugs has been reported to improve both survival rates and quality of life.
As for HAM/TSP, a neurological disorder caused by HTLV, there are scarce effective treatment options, and the primary aim is to manage symptoms. Corticosteroids, a type of anti-inflammatory medicine, are often used and might slightly slow the disease progression. A monoclonal antibody treatment (mogamulizumab), has been used in Japan, with some patients reporting decreased spasticity (muscle stiffness) and improved motor function. However, treatments aimed at fighting the virus itself haven’t been able to change the course of the disease effectively.
What else can Human T-Cell Lymphotropic Virus be?
Pinpointing the precise cause of illnesses like ATLL (Adult T-cell Leukemia/Lymphoma) or HAM/TSP (HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis) can be no easy task due to their similarity with other diseases. For instance, ATLL can closely resemble other types of T-cell cancers. It can appear similar to cutaneous T-cell lymphoma (a cancer affecting the skin) in terms of visible characteristics and cell behavior. Sometimes, ATLL might even cause lymph nodes to swell and take on an appearance akin to Hodgkin’s disease, a type of lymphoma. Certain cells, known as ‘flower cells’, are unique to ATLL and can be identified by examining the patient’s blood. But, sorting out these cases from mild or ‘smoldering’ forms of ATLL can be tricky, and might require additional tests like PCR to identify specific cell changes associated with ATLL.
When it comes to HAM/TSP, a disease that affects nerve cells, the primary challenge is distinguishing it from multiple sclerosis (MS). This task is especially difficult in cases where the patient hails from an area where HTLV-1, the virus that causes HAM/TSP, is common. Identifying the presence of this virus in the patient’s cerebrospinal fluid (fluid in the brain and spinal cord) is crucial for securing an accurate diagnosis. Furthermore, HTLV-1 seems to have the potential to cause a variety of neurological conditions such as amyotrophic lateral sclerosis (a motor neuron disease) and conus medullaris syndrome (a condition affecting the lower part of the spinal cord). Establishing a concrete cause-and-effect relationship between these conditions and HTLV-1, though, can be a tough challenge.
What to expect with Human T-Cell Lymphotropic Virus
The course and outcome of HTLV-1 infection can be quite unpredictable. This type of infection often starts unnoticed and can happen early in life, typically passed from mother to child. It can take a long time, varying from person to person, for this infection to develop into a disease. This suggests that just having the virus isn’t enough to cause disease; there might be other factors involved, but we don’t fully understand them yet. Therefore, it’s hard to predict how HTLV-1 infection will progress.
ATLL, a disease linked with HTLV-1, has a very poor outcome. It’s deadly and difficult to treat. Usually, the body’s immune system is weak, making the disease hard to fight off. The outcome of ATLL depends on the type of disease, although, the most common type, known as ‘acute’, generally leads to the worst survival rate. A study in the US that looked at 195 ATLL patients over 16 years found that, on average, those with acute ATLL lived for 4 months, those with lymphomatous ATLL lived for 10 months, and those with chronic or smoldering ATLL lived for 72 months. It’s noteworthy that although chronic/smoldering ATLL has a relatively better outcome, it only applies to a small group that makes up 6% of all patients in the study.
Another disease associated with HTLV-1 is HAM/TSP. This disease’s progression is highly variable, and there are limited ways to predict how quickly the disease will progress based on the amount of the virus in the body. Most patients experience slow progression, but a small group can deteriorate quickly and require the use of a wheelchair. On the other hand, some patients maintain nearly normal nerve function and only have mild difficulty standing up from a chair without help.
Possible Complications When Diagnosed with Human T-Cell Lymphotropic Virus
The HTLV-1 virus usually doesn’t show any symptoms when a person is first infected. However, it can lead to severe health problems and sometimes even death in about 5% of people who have it. These health issues, like ATLL and HAM/TSP, often show up years or decades after the person first got the virus, which can lead to a delay in diagnosing and treating the related disease. The health problems that come from the HTLV-1 virus can seriously impact a person’s quality of life, but it’s still unclear how we can predict when these health problems will start, get worse, or best treat them.
Common Issues:
- Delayed diagnosis due to the virus being asymptomatic during the first infection
- Severe health problems like ATLL and HAM/TSP
- Unpredictability of disease onset and progression
- Uncertainty in optimal treatment approaches
Preventing Human T-Cell Lymphotropic Virus
Many people don’t know much about HTLV-1 (Human T-cell lymphotropic virus type 1), even in areas where many people have it. HTLV-1 is a virus that can be passed from person to person. Certain people, like sex workers and people who use drugs with needles, are more likely to get HTLV-1. Unfortunately, these people also often have trouble getting healthcare.
This means that there is a big opportunity to teach people about how HTLV-1 is passed from person to person. For example, a mother can pass the virus to her child while breastfeeding. The virus can also be passed through sex and by sharing needles. Knowing this can help stop the spread of HTLV-1.