Long terminal repeat circular DNA as markers of active viral replication of human t lymphotropic Virus-1 in vivo

James M. Fox, Silva Hilburn, Maria Antonietta Demontis, David W. Brighty, Maria Fernanda Rios Grassi, Bernardo Galvão-Castro, Graham P. Taylor, Fabiola Martin (Lead / Corresponding author)

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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.

    Original languageEnglish
    Article number80
    Pages (from-to)1-15
    Number of pages15
    JournalViruses
    Volume8
    Issue number3
    DOIs
    Publication statusPublished - 14 Mar 2016

    Keywords

    • HTLV
    • Human T-lymphotropic virus
    • Long terminal repeat
    • LTR DNA circles
    • Viral replication

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    Fox, J. M., Hilburn, S., Demontis, M. A., Brighty, D. W., Grassi, M. F. R., Galvão-Castro, B., Taylor, G. P., & Martin, F. (2016). Long terminal repeat circular DNA as markers of active viral replication of human t lymphotropic Virus-1 in vivo. Viruses, 8(3), 1-15. [80]. https://doi.org/10.3390/v8030080