Torque Teno Virus (TTV)

Scientists from all over the world have been trying to understand a virus called torque teno virus/transfusion-transmitted virus (TTV) for about 20 years now. TTV is often found in patients with different types of viral hepatitis, cases of hepatitis without a known viral cause, and even in healthy individuals. It was first discovered by Japanese researchers in 1997 by using a PCR assay.

In 2009, a group of virus experts called the International Committee on Taxonomy of Viruses (ICTV) gave the virus an official name. They chose the name based on how it usually spreads (through blood transfusions) and its unique genetic structure called “torque teno.” The virus belongs to a family called Circoviridae, specifically the Anelloviridae group in the Alphatorquevirus category. There are also other groups called Betatorquevirus and Gammatorquevirus. Since it was first discovered, scientists have found similar viruses related to this one, like torque teno mini virus (TTMV) and torque teno midi virus (TTMDV), and they all have some differences in their genetic material.

Epidemiology

TTV is found in many people around the world, with some regions having a high prevalence of 95% in healthy individuals. The presence of TTV can vary among different geographic regions and populations. For example, African descent populations have a higher detection rate of TTV DNA compared to Europe’s indigenous people. Asian countries like China, Pakistan, Iran, and Qatar also show a high prevalence of the virus.

Recent studies have reported a higher frequency of TTV presence in populations compared to earlier studies, possibly due to more accurate detection methods (e.g., PCR) being used. TTV is known as a ubiquitous virus because of its widespread presence in the population and its ability to infect different tissues.

Symptoms

While TTV does not typically cause hepatitis symptoms by itself, it is frequently detected in individuals with liver disease. In general, TTV infection is thought to occur without causing noticeable symptoms.

Routes of Transmission

TTV can be transmitted from an infected person through different routes.

Parenteral route: TTV has a high affinity for the liver, so the parenteral route (involving direct entry into the bloodstream) is considered a likely mode of transmission. This includes infection through contaminated blood transfusions, hemodialysis procedures, and injections. People at higher risk for TTV infection are blood donors, hemophilic patients, those who receive multiple blood transfusions, patients undergoing hemodialysis, organ transplant recipients, and intravenous drug users.

Horizontal route: This includes transmission through contaminated food, water, and close contact. Most infections occur through non-parenteral routes, like the fecal-oral route, which explains why TTV is widespread among healthy individuals, especially in older age groups. Infection through the gastrointestinal tract can be observed by high levels of viral DNA in bile, saliva, and feces, which are higher than in the blood. Experimental evidence supports transmission through the fecal-oral and parenteral routes, such as contaminated blood transfusions.

Vertical transmission route: This involves the possible transfer of infection from an infected mother to her fetus during pregnancy and through breastfeeding. Studies suggest that TTV infection can occur during pregnancy. It is estimated that around 99% of babies born to infected mothers have TTV antibodies.

Sexual transmission route: TTV DNA has been detected in bodily fluids like semen, vaginal secretions, cervical mucus, and saliva, which can come into contact during sexual intercourse. Both partners in a sexual relationship can have TTV, indicating sexual transmission. The prevalence of TTV in the group at risk for sexual transmission is similar to that in the general population.

Diagnosis

TTV can be found in many parts of the body, such as tissues, cells, and body fluids, except for red blood cells and platelets. It has been found in various bodily fluids like saliva, sweat, bile, semen, urine, feces, nasal and vaginal secretions, and scrapings from the back of the nose and throat. It multiplies in certain types of cells like mononucleocytes, liver cells, bone marrow cells, and certain blood cells, especially T lymphocytes. To diagnose a TTV infection, doctors can examine biopsy samples taken from the liver, lymph nodes, bone marrow, spleen, pancreas, lungs, and thyroid gland and run some tests like polymerase chain reaction (PCR) assays and immunoassays.

When the TTV virus multiplies and triggers the body’s immune response, it leads to the production of immunoglobulins, which are important for fighting against viruses. To determine the presence and quantity of antibodies against TTV in biological samples, immune assays are used. After TTV infection, the first antibodies to appear in the blood usually show up 10 to 21 weeks after infection, but then start to decrease and gradually disappear within 5 to 11 weeks. Another type of antibody emerges at around 16 weeks after infection and reaches its highest levels at 5 months of persistent virus presence. Researchers suggest that the presence of anti-TTV antibodies in the blood can be a sign of past infection.

Researchers in Belarus studied the detection rate of TTV, TTMDV, and TTMV in patients with chronic liver diseases and those without any signs of liver problems or viral hepatitis. The methods used to detect TTV DNA greatly influence its identification. Factors like the type of sample tested (such as plasma or whole blood) and the specific PCR assays or primers used can affect the detection of TTV DNA. Different studies have shown varying prevalence rates based on the detection methods used. Initially, scientists used specific primers to amplify a region called N22-ORF1 for diagnosing TTV infection. However, this region can vary a lot in the genetic material of the virus so using it for amplification might result in a lower detection rate for TTV. Instead, another region called UTR (untranslated region), which is more stable across different virus types, is now commonly used for detecting TTV infection.

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