Transfusion transmitted virus

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Transfusion Transmitted Virus
Virus classification
Group II (ssDNA)

Transfusion Transmitted Virus

TT virus (TTV) was the first member of the new family Anelloviridae to be discovered.


TTV, for transfusion transmitted virus or torque teno virus was first reported in a Japanese patient in 1997 by the research scientist T. Nishizawa;[1] the virus 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.[2] For the most part, TTV infection is believed to be asymptomatic.

Initially found in Japanese patients with hepatitis of unknown cause, 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).[3] At that time, sequence analysis suggested that TTV was related to the Parvoviridae family. At the end of 1998, two independent studies demonstrated the presence of an additional GC-rich region of about 120 nt which led to the discovery of the circular nature of the TTV genome (~3800 nt); this finding established the relationship of TTV with the Circoviridae family.[4]


Initially the virus was named TTV after a patient with T.T. initials. Later the name torque (necklace) teno (from Latin tenuis - "thin") virus was adopted as it preserved the original abbreviation.[5]

Viral spread[edit]

The large number of epidemiological studies permitted to clearly point out the global distribution of the virus (Africa, 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,[6] 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.[7] Sexual transmission has also been proposed.[8]

Related viruses have been found in chimpanzees, apes, African monkeys, tupaias, chickens, pigs, cows, sheep and dogs.[9]

Vertical transmission has been reported in pigs.[10][11]


TTV's genome is a negative sense, circular 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 frames, encoding 770 and 202 amino acids, 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.


These viruses are not currently believed to cause disease in humans. Infection with these viruses tends to lead to lifelong viraemia and their possible 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%);[12] the presence of multiple genotypes was common.

The presence of this virus in acute lung injury and exacerbations of idiopathic lung fibrosis has been reported.[13]

Increased viral loads in cases of congenital mannose-binding lectin deficiencies have been reported.[14]

A possible case of aplastic anaemia with hepatitis has been reported.[15]

One case of post transplant hepatitis has been reported.[16]

An association with head/neck cancer has been proposed.[17]


Not much is known about TTV's replication, however based on animal circoviral studies, a double strand replication structure appears necessary; some studies have described the presence of double strand TTV DNA in various tissues and organs suggesting an active replication in these localizations.[18] These findings also minimize the hypothetic implication of TTV in hepatic disorders. No other data are at the present time available for TLMV (TTV-like Mini Virus; the strain infecting humans).


  1. ^ Nishizawa, T; Okamoto, H; Konishi, K; Yoshizawa, H; Miyakawa, Y; Mayumi, M (8 December 1997). "A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology". Biochemical and Biophysical Research Communications. 241 (1): 92–7. doi:10.1006/bbrc.1997.7765. PMID 9405239.
  2. ^ Biagini, P: "Human circoviruses.", pages 95-101. Veterinary Microbiology, 2004.
  3. ^ Nishizawa, T.; Okamoto, H.; Konishi, K.; Yoshizawa, H.; Miyakawa, Y.; Mayumi, M. (1997). "A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology". Biochem. Biophys. Res. Commun. 241: 92–97. doi:10.1006/bbrc.1997.7765. PMID 9405239.
  4. ^ Miyata, H.; Tsunoda, H.; Kazi, A.; Yamada, A.; Khan, M.A.; Yeung, B.J.; Murakami, J.; Kamahora, T.; Shiraki, K.; Hino, S. (1999). "Identification of a novel GC-rich 113-nucleotide region to complete the circular, single-stranded DNA genome of TT virus, the first human circovirus". J. Virol. 73: 3582–3586. PMID 10196248.
  5. ^ "AABB website" (PDF). Retrieved 25 December 2017.
  6. ^ Biagini, P.; Gallian, P.; Cantaloube, J.F.; De Micco, P.; de Lamballerie, X. (1998). "Presence of TT virus in French blood donors and intravenous drug users". J. Hepatol. 29: 684–685. doi:10.1016/s0168-8278(98)80167-0.
  7. ^ Gallian, P.; Biagini, P.; Zhong, S.; Louinssi, M.; Yeo, W.; Cantaloube, J.F.; Attoui, H.; de Micco, P.; Johnson, P.J.; de Lamballerie, X. (2000). "TT virus: a study of molecular epidemiology and transmission of genotypes 1, 2 and 3". J. Clin. Virol. 17: 43–49. doi:10.1016/s1386-6532(00)00066-4.
  8. ^ Zheng, MY; Lin, Y; Li, DJ; Ruan, HB; Chen, Y; Wu, TT (2010). "TTV and HPV co-infection in cervical smears of patients with cervical lesions in littoral of Zhejiang province". Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 24 (2): 110–112.
  9. ^ Hino, S; Miyata, H (2007). "Torque teno virus (TTV): current status". Rev Med Virol. 17 (1): 45–57. doi:10.1002/rmv.524.
  10. ^ Martínez-Guinó, L; Kekarainen, T; Segalés, J (2009). "Evidence of Torque teno virus (TTV) vertical transmission in swine". Theriogenology. 71 (9): 1390–1395. doi:10.1016/j.theriogenology.2009.01.010.
  11. ^ Pozzuto, T; Mueller, B; Meehan, B; Ringler, SS; McIntosh, KA; Ellis, JA; Mankertz, A; Krakowka, S (2009). "In utero transmission of porcine torque teno viruses". Vet Microbiol. 137 (3–4): 375–379. doi:10.1016/j.vetmic.2009.02.001.
  12. ^ Pinho-Nascimento, CA; Leite, JP; Niel, C; Diniz-Mendes, L (2011). "Torque teno virus in fecal samples of patients with gastroenteritis: Prevalence, genogroups distribution, and viral load". J Med Virol. 83 (6): 1107–11. doi:10.1002/jmv.22024.
  13. ^ Wootton SC, Kim DS, Kondoh Y, Chen E, Lee JS, Song JW, Huh JW, Taniguchi H, Chiu C, Boushey H, Lancaster LH, Wolters PJ, Derisi J, Ganem D, Collard HR (2011) Viral infection in acute exacerbation of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med.
  14. ^ Maggi F, Pifferi M, Michelucci A, Albani M, Sbranti S, Lanini L, Simi P, Macchia P, Pistello M, Bendinelli M (2011) Torque teno virus viremia load size in patients with selected congenital defects of innate immunity. Clin Vaccine Immunol. 18(4):692–694.
  15. ^ Ishimura M, Ohga S, Ichiyama M, Kusuhara K, Takada H, Hara T, Takahashi M, Okamoto H (2010) Hepatitis-associated aplastic anemia during a primary infection of genotype 1a torque teno virus. Eur J Pediatr. 2010 Jul;169(7):899–902
  16. ^ Piaggio F, Dodi F, Bottino G, Andorno E, Gentile R, Ferrari C, Barabino G, Giannone A, Immordino G, Miggino M, Magoni Rossi A, Moraglia E, Gasloli G, Gelli M, Ferrante R, Morelli N, Casaccia M, Valente U (2009) Torque Teno Virus—cause of viral liver disease following liver transplantation: a case report. Transplant Proc. 41(4):1378–1379
  17. ^ Hettmann, A; Demcsák, A; Bach, Á; Decsi, G; Dencs, Á; Pálinkó, D; Rovó, L; Nagy, K; Minarovits, J; Takács, M (2016). "Detection and phylogenetic analysis of Torque Teno Virus in salivary and tumor biopsy samples from head and neck carcinoma patients". Intervirology. 59 (2): 123–129. doi:10.1159/000452974.
  18. ^ Okamoto, H.; Nishizawa, T.; Takahashi, M.; Asabe, S.; Tsuda, F.; Yoshikawa, A. (2001a). "Heterogeneous distribution of tt virus of distinct genotypes in multiple tissues from infected humans". Virology. 288: 358–368. doi:10.1006/viro.2001.1097. PMID 11601907.