Background
Human T-cell leukemia virus type 1 (HTLV-1), classified in the retroviral family, is the earliest discovered human retrovirus and has infected 5 to 10 million people. People infected with HTLV-1 are at potential risk for fatal diseases, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraplegia (HAM/TSP). There are three main routes of HTLV-1 transmission, mother-to-child transmission through breastfeeding or childbirth, sexual contact, or contact through infected blood.
HTLV-1 belongs to the genus Deltaretrovirus, a human C-type retrovirus that mainly infects CD4 T lymphocytes. HTLV-1 can be classified into seven subtypes based on the analysis of the long terminal repeat (LTR) and env region, and the sequence variability among them is low. The HTLV-1 genome is encoded on two positive-sense single-stranded RNAs, and the single-stranded RNA is converted to double-stranded DNA, which is inserted into the DNA of the human host cell and integrated into the host genome to form a persistent infection. Cell-to-cell spread of HTLV-1 may predominate during early infection, leading to polyclonal infection of CD4 and CD8 T lymphocytes. HTLV-1 infection after established infection is maintained by clonal expansion of infected cells. The HTLV-1 genome encodes typical retroviral structural proteins (gag, pol, and env), the pX region of the genome encodes nonstructural regulatory proteins including p13, p12, p30, and p40 (Tax), and the complementary strand of pX encodes the HTLV-1 basic leucine zipper factor (HBZ), Tax and HBZ proteins are important for understanding the biology and pathogenesis of HTLV-1.
Figure 1. Structure of a mature HTLV-1 virion (A) and genetic composition of HTLV-1 (B)
(Source: Aghajanian S, et al. 2020)
HTLV-1 structural proteins are common targets for serologic testing, including Gag proteins and envelope glycoproteins. Serologic assays for gp46-I and gp46-II proteins differentiate HTLV-1 from HTLV-2 infection. The most widely used serologic test is the enzyme immunoassay (EIA), which is sensitive, simple, and high throughput, and is commonly used in epidemiologic investigations and blood. However, the specificity of EIA is low, and antigenic cross-reactivity with other pathogens or self-antigens may lead to false-positive results. Molecular assays for the detection of HTLV-1 nucleic acid sequences in peripheral blood and tissues by PCR are highly specific, and such assays target DNA proviruses integrated into the host cell genome and include qualitative, quantitative real-time, and droplet digital methods.
Alternative Names
Human T-cell leukemia virus type-I/II p19 Antigen ELISA
References
- 1. Aghajanian S, et al. Immunopathogenesis and Cellular Interactions in Human T-Cell Leukemia Virus Type 1 Associated Myelopathy/Tropical Spastic Paraparesis. Front Microbiol. 2020 Dec 22;11:614940.
- 2. Legrand N, et al. Clinical and Public Health Implications of Human T-Lymphotropic Virus Type 1 Infection. Clin Microbiol Rev. 2022 Apr 20;35(2):e0007821.
References
Mouse Models for HTLV-1 Infection and Adult T Cell Leukemia
Int J Mol Sci
Authors: Nakajima S, Okuma K.
Abstract
Adult T cell leukemia (ATL) is an aggressive hematologic disease caused by human T cell leukemia virus type 1 (HTLV-1) infection. Various animal models of HTLV-1 infection/ATL have been established to elucidate the pathogenesis of ATL and develop appropriate treatments. For analyses employing murine models, transgenic and immunodeficient mice are used because of the low infectivity of HTLV-1 in mice. Each mouse model has different characteristics that must be considered before use for different HTLV-1 research purposes. HTLV-1 Tax and HBZ transgenic mice spontaneously develop tumors, and the roles of both Tax and HBZ in cell transformation and tumor growth have been established. Severely immunodeficient mice were able to be engrafted with ATL cell lines and have been used in preclinical studies of candidate molecules for the treatment of ATL. HTLV-1-infected humanized mice with an established human immune system are a suitable model to characterize cells in the early stages of HTLV-1 infection. This review outlines the characteristics of mouse models of HTLV-1 infection/ATL and describes progress made in elucidating the pathogenesis of ATL and developing related therapies using these mice.
Adult T-cell leukemia/lymphoma in HTLV-1 non-endemic regions
J Clin Virol
Authors: de Mendoza C, Rando A, Miró E, Pena MJ, Rodríguez-Avial I, Ortega D, González-Praetorius A, Reina G, Pintos I, Pozuelo MJ, Soriano V; Spanish HTLV Network.
Abstract
Background: HTLV-1 infection is a neglected disease, despite producing neurological and lymphoproliferative severe illnesses and affect over 10 million people worldwide. Roughly 5% of HTLV-1 carriers develop Adult T-cell leukemia/lymphoma (ATLL), one of the most aggressive hematological malignancies.
Methods: A national HTLV-1 register exists since 1989 in Spain, a non-endemic country with a large migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic. The main features of all patients diagnosed with ATLL in Spain up to date are reported.
Results: A total of 451 cases of HTLV-1 infection had been reported in Spain until the end of year 2022. ATLL had been diagnosed in 35 (7.8%). The current average incidence of ATLL in Spain is of two cases per year. Women represent 57% of ATLL patients. Mean age at diagnosis was 47 years-old. Roughly 57% were Latin Americans and 26% Africans. At diagnosis, the majority presented with acute or lymphoma clinical forms. Survival was shorter than one year in most of them. Mean HTLV-1 proviral load was significantly greater in ATLL patients than in asymptomatic HTLV-1 carriers (2,305 vs 104 copies/104 PBMC). HTLV-1 subtyping in 6 ATLL patients found the 1a transcontinental variant (n = 4) and the Japanese variant (n = 2). All ATLL patients were negative for HIV-1, did not develop HTLV-1-associated myelopathy and were not transplant recipients.
Conclusion: The rate of ATLL is very low in Spain and mostly associated to migrants from HTLV-1 endemic regions. Given the poor clinical outcome of ATLL, HTLV-1 testing should be performed at least once in all migrants coming from HTLV-1 endemic countries and in natives who have lived in or had sex partners from such regions.
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