期刊
VIRUSES-BASEL
卷 8, 期 3, 页码 -出版社
MDPI AG
DOI: 10.3390/v8030080
关键词
long terminal repeat; human T-lymphotropic virus; viral replication; HTLV; LTR DNA circles
类别
资金
- University of York
- Hull York Medical School pump priming fund
- Wellcome Trust [092430/Z/10/Z]
- Imperial NIHR Biomedical Research Centre (BRC)
- Fundacao de Amparo a Pesquisa do Estado da Bahia (FAPESB)
- Brazilian National Council of Technological and Scientific Development (CNPq)
- Leukaemia and Lymphoma Research (LLR) [LLR 12041, LLR 09006]
- Wellcome Trust [092430/Z/10/Z] Funding Source: Wellcome Trust
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.
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