HTLV-1, the Other Pathogenic Yet Neglected Human Retrovirus: From Transmission to Therapeutic Treatment

Abstract

Going back to their discovery in the early 1980s, both the Human T-cell Leukemia virus type-1 (HTLV-1) and the Human Immunodeficiency Virus type-1 (HIV-1) greatly fascinated the virology scene, not only because they were the first human retroviruses discovered, but also because they were associated with fatal diseases in the human population. In almost four decades of scientific research, both viruses have had different fates, HTLV-1 being often upstaged by HIV-1. However, although being very close in terms of genome organization, cellular tropism, and viral replication, HIV-1 and HTLV-1 are not completely commutable in terms of treatment, especially because of the opposite fate of the cells they infect: death versus immortalization, respectively. Nowadays, the antiretroviral therapies developed to treat HIV-1 infected individuals and to limit HIV-1 spread among the human population have a poor or no effect on HTLV-1 infected individuals, and thus, do not prevent the development of HTLV-1-associated diseases, which still lack highly efficient treatments. The present review mainly focuses on the course of HTLV-1 infection, from the initial infection of the host to diseases development and associated treatments, but also investigates HIV-1/HTLV-1 co-infection events and their impact on diseases development.

Keywords: ATLL; HIV-1; HTLV-1; TSP/HAM; treatments; viral transmission.

Figure 1

The course of HTLV-1 (Human T-cell Leukemia Virus type-1) infection. (A) HTLV-1 transmission through sexual intercourse, breastfeeding or contaminated blood products will allow the dissemination of HTLV-1 infected cells at the vicinity of dendritic cells, which are then able to transmit HTLV-1 viruses to CD4+ T-cells; (B) Neo-infection of CD4+ T-cells, which requires a cell-cell contact between an infected and a non-infected T-cell, is achieved through cellular conduits, the viral synapse or the viral biofilm; (C) Tax expression in HTLV-1 infected cells will result in consequent cell signaling alterations, such as continuous proliferation and apoptosis inhibition. Immortalized HTLV-1 infected cells will then proliferate through mitotic divisions, also known as clonal expansion; (D) TSP/HAM (Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy) is an inflammatory-related disease, which appears in 1 to 2% of infected individuals. The production of IFN-γ (Interferon- gamma), by HTLV-1 infected cells and HTLV-1 specific cytotoxic cells infiltrated in the cerebrospinal fluid, will lead to neural tissue damages, both directly by exacerbating inflammatory responses and indirectly by recruiting more IFN-γ producing cells in the CSF (Cerebrospinal fluid) through CXCL10 (C-X-C motif chemokine ligand 10) expression by astrocytes. (E) ATLL (Adult T-cell Leukemia/Lymphoma) is an immunosuppressed-related disease, which appears in 2 to 4% of infected individuals. The accumulation of genetic alterations in HTLV-1 infected T-cells leads to their transformation, and subsequent loss of Tax expression, either by mutations in the Tax gene or genetic modifications of the proviral 5′ LTR (Long Terminal Repeat). HTLV-1 transformed cells can escape from CTL (Cytotoxic T-cell) responses, through the loss of viral antigens presentation to the T-cell receptor, the production of Th1 (T-helper 1) inhibitory cytokines, and the recruitment of regulatory T-cells via CCL22 (C-C motif chemokine ligand 22) expression; (F) Current options to treat patients with TSP/HAM or ATLL.