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

Switzer, WM and Qari, SH and Wolfe, ND and Burke, DS and Folks, TM and Heneine, W (2006) Ancient origin and molecular features of the novel human T-lymphotropic virus type 3 revealed by complete genome analysis. Journal of Virology, 80 (15). 7427 - 7438. ISSN 0022-538X

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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. Copyright © 2006, American Society for Microbiology. All Rights Reserved.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Switzer, WM
Qari, SH
Wolfe, ND
Burke, DSdonburke@pitt.eduDONBURKE
Folks, TM
Heneine, W
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 1 August 2006
Date Type: Publication
Journal or Publication Title: Journal of Virology
Volume: 80
Number: 15
Page Range: 7427 - 7438
DOI or Unique Handle: 10.1128/jvi.00690-06
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
ISSN: 0022-538X
Date Deposited: 07 May 2015 20:41
Last Modified: 02 Feb 2019 16:57
URI: http://d-scholarship.pitt.edu/id/eprint/24351

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