Please use this identifier to cite or link to this item: http://www.arca.fiocruz.br/handle/icict/14305
Title: Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo
Authors: Fox, James M
Hilburn, Silva
Demontis, Maria-Antonietta
Brighty, David W
Grassi, Maria Fernanda Rios
Castro Filho, Bernardo Galvão
Taylor, Graham P
Martin, Fabiola
Affilliation: University of York. Centre for Immunology and Infection. Department of Biology & Hull York Medical School. York, UK
Imperial College. Section of Infectious Diseases. Department of Medicine. London, UK
Imperial College. Section of Infectious Diseases. Department of Medicine. London, UK / The National Centre for Human Retrovirology/HTLV Clinic. Imperial College Healthcare NHS Trust St Mary’s Hospital. London NY, UK
University of Dundee. Division of Cancer Research. Ninewells Hospital & Medical School. Dundee, UK
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil
HTLV-Centre Bahian School of Medicine. Salvador, Bahia, Brasil
Imperial College. Section of Infectious Diseases. Department of Medicine. London, UK / The National Centre for Human Retrovirology/HTLV Clinic. Imperial College Healthcare NHS Trust St Mary’s Hospital. London NY, UK
University of York. Centre for Immunology and Infection. Department of Biology & Hull York Medical School. York, UK
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.
Keywords: Long terminal repeat
LTR DNA circles
Human T-lymphotropic virus
HTLV
Viral replication
Issue Date: 2016
Publisher: MDPI
Citation: FOX, J. M. et al. Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo. Viruses, v. 8, p. 80, 2016.
ISSN: 1999-4915
10.3390/v8030080
Copyright: open access
Appears in Collections:IGM - Artigos de Periódicos

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