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Long terminal repeat circular DNA as markers of active viral replication of human T lymphotropic virus-1 in vivo
File(s)
viruses-08-00080.pdf (976.53 KB)
Published version
Author(s)
Fox, JM
Hilburn, S
Demontis, MA
Brighty, DW
Rios Grassi, MF
Type
Journal Article
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.
Date Issued
2016-03-14
Date Acceptance
2016-03-04
Citation
Viruses, 2016, 8 (3)
URI
DOI
ISSN
1999-4915
Publisher
MDPI
Journal / Book Title
Viruses
Volume
8
Issue
3
Copyright Statement
© 2016 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution
(CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
PII: v8030080
Subjects
HTLV
LTR DNA circles
human T-lymphotropic virus
long terminal repeat
viral replication
Publication Status
Published