Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo
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 b...
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| Format: | Article |
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MDPI AG
2016-03-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/8/3/80 |
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| author | James M Fox Silva Hilburn Maria-Antonietta Demontis David W Brighty Maria Fernanda Rios Grassi Bernardo Galvão-Castro Graham P Taylor Fabiola Martin |
| author_facet | James M Fox Silva Hilburn Maria-Antonietta Demontis David W Brighty Maria Fernanda Rios Grassi Bernardo Galvão-Castro Graham P Taylor Fabiola Martin |
| author_sort | James M Fox |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T10:31:10Z |
| format | Article |
| id | doaj.art-32cd01e058f34cd8bbc456182a65af4b |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-22T10:31:10Z |
| publishDate | 2016-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-32cd01e058f34cd8bbc456182a65af4b2022-12-21T18:29:19ZengMDPI AGViruses1999-49152016-03-01838010.3390/v8030080v8030080Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in VivoJames M Fox0Silva Hilburn1Maria-Antonietta Demontis2David W Brighty3Maria Fernanda Rios Grassi4Bernardo Galvão-Castro5Graham P Taylor6Fabiola Martin7Centre for Immunology and Infection, Department of Biology & Hull York Medical School, University of York, York YO10 5DD, UKSection of Infectious Diseases, Department of Medicine, Imperial College, London W2 1PG, UKSection of Infectious Diseases, Department of Medicine, Imperial College, London W2 1PG, UKDivision of Cancer Research, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UKOswaldo Cruz Foundation, Gonçalo Moniz Research Center-BA, Advanced Laboratory of Public Health, Salvador, Bahia, Candeal 40296-710, BrazilHTLV-Centre Bahian School of Medicine, Salvador, Bahia 40050-420, BrazilSection of Infectious Diseases, Department of Medicine, Imperial College, London W2 1PG, UKCentre for Immunology and Infection, Department of Biology & Hull York Medical School, University of York, York YO10 5DD, UKClonal 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.http://www.mdpi.com/1999-4915/8/3/80long terminal repeatLTR DNA circleshuman T-lymphotropic virusHTLVviral replication |
| spellingShingle | James M Fox Silva Hilburn Maria-Antonietta Demontis David W Brighty Maria Fernanda Rios Grassi Bernardo Galvão-Castro Graham P Taylor Fabiola Martin Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo Viruses long terminal repeat LTR DNA circles human T-lymphotropic virus HTLV viral replication |
| title | Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo |
| title_full | Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo |
| title_fullStr | Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo |
| title_full_unstemmed | Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo |
| title_short | Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo |
| title_sort | long terminal repeat circular dna as markers of active viral replication of human t lymphotropic virus 1 in vivo |
| topic | long terminal repeat LTR DNA circles human T-lymphotropic virus HTLV viral replication |
| url | http://www.mdpi.com/1999-4915/8/3/80 |
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