Ancient origin and molecular features of the novel human T-lymphotropic virus type 3 revealed by complete genome analysis

William M. Switzer, Shoukat H. Qari, Nathan D. Wolfe, Donald S. Burke, Thomas M. Folks, Walid Heneine

Research output: Contribution to journalArticle

Abstract

Human T-lymphotropic virus type 3 (HTLV-3) is a new virus recently identified in two primate hunters in Central Africa. Limited sequence analysis shows that HTLV-3 is distinct from HTLV-1 and HTLV-2 but is genetically similar to simian T-lymphotropic virus type 3 (STLV-3). We report here the first complete HTLV-3 sequence obtained by PCR-based genome walking using uncultured peripheral blood lymphocytes from an HTLV-3-infected person. The HTLV-3 (2026ND) genome is 8,917 bp long and is genetically equidistant from HTLV-1 and HTLV-2, sharing about 62% identity. Phylogenetic analysis of all gene regions confirms this relationship and shows that HTLV-3 falls within the diversity of STLV-3, suggesting a primate origin. However, HTLV-3 (2026ND) is unique, sharing only 87% to 92% sequence identity with STLV-3. SimPlot and phylogenetic analysis did not reveal any evidence of genetic recombination with either HTLV-1, HTLV-2, or STLV-3. Molecular dating estimates that the ancestor of HTLV-3 is as old as HTLV-1 and HTLV-2, with an inferred divergence time of 36,087 to 54,067 years ago. HTLV-3 has a prototypic genomic structure, with all enzymatic, regulatory, and structural proteins preserved. Like STLV-3, HTLV-3 is missing a third 21-bp transcription element found in the long terminal repeats of HTLV-1 and HTLV-2 but instead contains a unique activator protein-1 transcription factor upstream of the 21-bp repeat elements. A PDZ motif, like that in HTLV-1, which is important for cellular signal transduction and transformation, is present in the C terminus of the HTLV-3 Tax protein. A basic leucine zipper region located in the antisense strand of HTLV-1, believed to play a role in viral replication and oncogenesis, was also found in the complementary strand of HTLV-3. The ancient origin of HTLV-3, the broad distribution of STLV-3 in Africa, and the propensity of STLVs to cross species into humans all suggest that HTLV-3 may be prevalent and support the need for expanded surveillance for this virus.

Original languageEnglish (US)
Pages (from-to)7427-7438
Number of pages12
JournalJournal of Virology
Volume80
Issue number15
DOIs
StatePublished - Aug 2006

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Simian T-lymphotropic virus 3
HIV
Genome
viruses
Human T-lymphotropic virus 1
genome
Primate T-lymphotropic virus 1
Human T-lymphotropic virus 2
Primate T-lymphotropic virus 2
Primates
tax Gene Products
Primate T-lymphotropic virus 3
Viruses
Central Africa
Leucine Zippers
Terminal Repeat Sequences
Transcription Factor AP-1
Genetic Recombination
genome walking
Walking

ASJC Scopus subject areas

  • Immunology

Cite this

Ancient origin and molecular features of the novel human T-lymphotropic virus type 3 revealed by complete genome analysis. / Switzer, William M.; Qari, Shoukat H.; Wolfe, Nathan D.; Burke, Donald S.; Folks, Thomas M.; Heneine, Walid.

In: Journal of Virology, Vol. 80, No. 15, 08.2006, p. 7427-7438.

Research output: Contribution to journalArticle

Switzer, William M. ; Qari, Shoukat H. ; Wolfe, Nathan D. ; Burke, Donald S. ; Folks, Thomas M. ; Heneine, Walid. / Ancient origin and molecular features of the novel human T-lymphotropic virus type 3 revealed by complete genome analysis. In: Journal of Virology. 2006 ; Vol. 80, No. 15. pp. 7427-7438.
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