Transfusion Transmitted Virus
Encyclopedia
TT virus was the first member of the new family Anelloviridae to be discovered.
is extremely common, even in healthy individuals — as much as 100% prevalent in some countries, and in approximately 10% of blood donors in the UK and the US. Although it does not appear to cause symptoms of hepatitis
on its own, it is often found in patients with liver disease. For the most part, TTV infection is believed to be asymptomatic
.
family. At the end of 1998, two independent studies demonstrated the presence of an additional GC-rich region of about 120 nt which lead to the discovery of the circular nature of the TTV genome (~3800 nt). This finding permitted to establish the relationship of TTV with the Circoviridae
family.
, North
and South America
, Asia
, Europe
, Oceania
) in rural and urban populations. Despite that the link between TTV infection and a given pathology has not been shown, the hypothesis of a relation between viral load and the immune status of the host was suggested. Moreover, although initially suspected to be transmitted only by blood transfusion, the global dispersion of the virus in populations and its detection in various biologic samples (plasma, saliva, feces, etc...) suggest combined modes of diffusion, and in particular the spread by saliva droplets. Sexual transmission has also been proposed.
Related viruses have been found in chimpanzees, apes, African monkeys, tupaias, chickens, pigs, cows, sheep and dogs.
Vertical transmission has been reported in pigs.
is a single-stranded piece of DNA
, approximately 3.8 kb in length; it is a non-enveloped virus with a virion of about 40 nm in diameter. While bearing some similarity to members of the group Circoviridae
, it lacks sequence homology with any known viruses, and it is believed to be the first known member of a new family of viruses. It is classified under the family Anelloviridae.
Its genome contains 2 large open reading frame
s, encoding 770 and 202 amino acid
s, as well as several smaller ORFs. The genomic region -154/-76 contains a critical promoter.
Isolates have been classified into five main clades numbered 1 to 5. TTV genogroup 3 also includes the 8 virus strains known as SENV-A to H.
Examination of faecal samples in 135 Brazilians with gastroenteritis showed evidence of the virus in 121 (91%). The presence of multiple genotypes was common.
The presence of this virus in acute lung injury and exerbations of idiopathic lung fibrosis has been reported.
Increased viral loads in cases of ongenital mannose-binding lectin deficiencies have been reported.
A possible case of aplastic anaemia with hepatitis has been reported.
One case of post transplant hepatitis has been reported.
Initial discovery
TTV, for Transfusion Transmitted Virus or Torque teno virus was first reported in a Japanese patient in 1997 by the research scientist T. Nishizawa. The virusVirus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
is extremely common, even in healthy individuals — as much as 100% prevalent in some countries, and in approximately 10% of blood donors in the UK and the US. Although it does not appear to cause symptoms of hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
on its own, it is often found in patients with liver disease. For the most part, TTV infection is believed to be asymptomatic
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...
.
History
Initially found in Japanese patients with hepatitis of unknown aetiology, TTV was detected in various populations without proven pathology, including blood donors. This new virus was initially discovered in 1997 by means of representational difference analysis (RDA) in the plasma of a Japanese patient (initials T.T.) with posttransfusion hepatitis. A sequence (N22) of 500 nucleotides (nt) was first characterized and further extended to about 3700 nt (TA278 clone). At that time, sequence analysis suggested that TTV was related to the ParvoviridaeParvoviridae
The Parvoviridae family includes the smallest known viruses, and some of the most environmentally resistant. They were discovered during the 1960s and affect vertebrates and insects...
family. At the end of 1998, two independent studies demonstrated the presence of an additional GC-rich region of about 120 nt which lead to the discovery of the circular nature of the TTV genome (~3800 nt). This finding permitted to establish the relationship of TTV with the Circoviridae
Circoviridae
The Circoviridae are a family of viruses. These are small, relatively poorly-studied viruses, with circular, single-stranded DNA genomes of approximately one to four kilobases-Virology:...
family.
Viral spread
The large number of epidemiological studies permitted to clearly point out the global distribution of the virus (AfricaAfrica
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
, North
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
and South America
South America
South America is a continent situated in the Western Hemisphere, mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. The continent is also considered a subcontinent of the Americas. It is bordered on the west by the Pacific Ocean and on the north and east...
, Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
, Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
, Oceania
Oceania
Oceania is a region centered on the islands of the tropical Pacific Ocean. Conceptions of what constitutes Oceania range from the coral atolls and volcanic islands of the South Pacific to the entire insular region between Asia and the Americas, including Australasia and the Malay Archipelago...
) in rural and urban populations. Despite that the link between TTV infection and a given pathology has not been shown, the hypothesis of a relation between viral load and the immune status of the host was suggested. Moreover, although initially suspected to be transmitted only by blood transfusion, the global dispersion of the virus in populations and its detection in various biologic samples (plasma, saliva, feces, etc...) suggest combined modes of diffusion, and in particular the spread by saliva droplets. Sexual transmission has also been proposed.
Related viruses have been found in chimpanzees, apes, African monkeys, tupaias, chickens, pigs, cows, sheep and dogs.
Vertical transmission has been reported in pigs.
Genome
TTV's genomeGenome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
is a single-stranded piece of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, approximately 3.8 kb in length; it is a non-enveloped virus with a virion of about 40 nm in diameter. While bearing some similarity to members of the group Circoviridae
Circoviridae
The Circoviridae are a family of viruses. These are small, relatively poorly-studied viruses, with circular, single-stranded DNA genomes of approximately one to four kilobases-Virology:...
, it lacks sequence homology with any known viruses, and it is believed to be the first known member of a new family of viruses. It is classified under the family Anelloviridae.
Its genome contains 2 large open reading frame
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...
s, encoding 770 and 202 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s, as well as several smaller ORFs. The genomic region -154/-76 contains a critical promoter.
Isolates have been classified into five main clades numbered 1 to 5. TTV genogroup 3 also includes the 8 virus strains known as SENV-A to H.
Clinical
These viruses are not currently believed to cause disease in humans. Infection with these viruses tends to lead to lifelong viraemia and their posible association with disease remains under investigation. Higher than usual viral loads have been associated with severe idiopathic inflammatory myopathies, cancer and lupus.Examination of faecal samples in 135 Brazilians with gastroenteritis showed evidence of the virus in 121 (91%). The presence of multiple genotypes was common.
The presence of this virus in acute lung injury and exerbations of idiopathic lung fibrosis has been reported.
Increased viral loads in cases of ongenital mannose-binding lectin deficiencies have been reported.
A possible case of aplastic anaemia with hepatitis has been reported.
One case of post transplant hepatitis has been reported.