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Viruses 2016, 8(3), 80; doi:10.3390/v8030080

Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo

1
Centre for Immunology and Infection, Department of Biology & Hull York Medical School, University of York, York YO10 5DD, UK
2
Section of Infectious Diseases, Department of Medicine, Imperial College, London W2 1PG, UK
3
The National Centre for Human Retrovirology/HTLV Clinic, Imperial College Healthcare NHS Trust, St Mary’s Hospital, London W2 1NY, UK
4
Division of Cancer Research, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UK
5
Oswaldo Cruz Foundation, Gonçalo Moniz Research Center-BA, Advanced Laboratory of Public Health, Salvador, Bahia, Candeal 40296-710, Brazil
6
HTLV-Centre Bahian School of Medicine, Salvador, Bahia 40050-420, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Louis M. Mansky
Received: 7 December 2015 / Revised: 24 February 2016 / Accepted: 4 March 2016 / Published: 14 March 2016
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Abstract

Clonal expansion of human T-lymphotropic virus type-1 (HTLV-1) infected cells in vivo is well documented. Unlike human immunodeficiency virus type 1 (HIV-1), HTLV-1 plasma RNA is sparse. The contribution of the “mitotic” spread of HTLV-1 compared with infectious spread of the virus to HTLV-1 viral burden in established infection is uncertain. Since extrachromosomal long terminal repeat (LTR) DNA circles are indicators of viral replication in HIV-1 carriers with undetectable plasma HIV RNA, we hypothesised that HTLV-1 LTR circles could indicate reverse transcriptase (RT) usage and infectious activity. 1LTR and 2LTR DNA circles were measured in HTLV-1 cell lines and peripheral blood mononuclear cells (PBMC) of asymptomatic carriers (ACs) and patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukaemia/lymphoma (ATLL). 1LTR DNA circles were detected in 14/20 patients at a mean of 1.38/100 PBMC but did not differentiate disease status nor correlate with HTLV-1 DNA copies. 2LTR DNA circles were detected in 30/31 patients and at higher concentrations in patients with HTLV-1-associated diseases, independent of HTLV-1 DNA load. In an incident case the 2LTR DNA circle concentration increased 2.1 fold at the onset of HAM/TSP compared to baseline. Detectable and fluctuating levels of HTLV-1 DNA circles in patients indicate viral RT usage and virus replication. Our results indicate HTLV-1 viral replication capacity is maintained in chronic infection and may be associated with disease onset. View Full-Text
Keywords: long terminal repeat; LTR DNA circles; human T-lymphotropic virus; HTLV; viral replication long terminal repeat; LTR DNA circles; human T-lymphotropic virus; HTLV; viral replication
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MDPI and ACS Style

Fox, J.M.; Hilburn, S.; Demontis, M.-A.; Brighty, D.W.; Rios Grassi, M.F.; Galvão-Castro, B.; Taylor, G.P.; Martin, F. Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo. Viruses 2016, 8, 80.

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