Transfusion Transmitted Virus

TT virus (TTV) corresponds to the first member of a new group species of circovirus infecting humans.

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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 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 ^[1]. For the most part, TTV infection is believed to be asymptomatic.

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) ^[2]. 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 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 ^[3].

Viral spread

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 ^[4], 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 ^[5].

Genome

TTV's genome 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 genus Anellovirus.

Its genome contains 2 large open reading frames, encoding 770 and 202 amino acids, as well as several smaller ORFs.

Replication

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 ^[6]. 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).

References

1. ^ Biagini, P: "Human circoviruses.", pages 95-101. Veterinary Microbiology, 2004.
2. ^ 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.
3. ^ 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.
4. ^ 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.
5. ^ 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.
6. ^ 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.