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Journal of Virology, April 2000, p. 2990-3000, Vol. 74, No. 7
Hepatitis Branch, Division of Viral and
Rickettsial Diseases, National Center for Infectious Diseases, Centers
for Disease Control and Prevention, U.S. Department of Health and Human
Services, Atlanta, Georgia1; Medical
University, Liaoning, China2; Institute
of Virology, Essen, Germany3; The
D. I. Ivanovsky Institute of Virology, Moscow,
Russia4; University of North Carolina,
Chapel Hill, North Carolina5; and Emory
University, Atlanta, Georgia6
Received 10 August 1999/Accepted 22 December 1999
TT virus (TTV) is a recently discovered infectious agent originally
obtained from transfusion-related hepatitis. However, the causative
link between the TTV infection and liver disease remains uncertain.
Recent studies demonstrated that genome sequences of different TTV
strains are significantly divergent. To assess genetic heterogeneity of
the TTV genome in more detail, a sequence analysis of PCR fragments
(271 bp) amplified from open reading frame 1 (ORF1) was performed. PCR
fragments were amplified from 5 to 40% of serum specimens obtained
from patients with different forms of hepatitis who reside in different
countries (e.g., China, Egypt, Vietnam, and the United States) and from
normal human specimens obtained from U.S. residents. A total of 170 PCR
fragments were sequenced and compared to sequences derived from the
corresponding TTV genome region deposited in GenBank. Genotypes 2 and 3 were found to be significantly more genetically related than any other TTV genotype. Moreover, three sequences were shown to be almost equally
related to both genotypes 2 and 3. These observations suggest a merger
of genotypes 2 and 3 into one genotype, 2/3. Additionally, five new
groups of TTV sequences were identified. One group represents a new
genotype, whereas the other four groups were shown to be more
evolutionary distant from all known TTV sequences. The evolutionary
distances between these four groups were also shown to be greater than
between TTV genotypes. The phylogenetic analysis suggested that these
four new genetic groups represent closely related yet different viral
species. Thus, TTV exists as a "swarm" of at least five closely
related but different viruses. These observations suggest a high degree
of genetic complexity within the TTV population. The finding of the
additional TTV-related species should be taken into consideration when
the association between TTV infections and human diseases of unknown
etiology is studied.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Sequence Heterogeneity of TT Virus and Closely
Related Viruses

*
Corresponding author. Mailing address: Hepatitis
Branch, MS A-33, Division of Viral and Rickettsial Diseases, National
Center for Infectious Diseases, Centers for Disease Control and
Prevention, 1600 Clifton Rd., Atlanta, GA 30333. Phone: (404) 639-2610. Fax: (404) 639-1563. E-mail address: yek0{at}cdc.gov.
Present address: Covance Central Laboratory Services Inc.,
Indianapolis, Ind.
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