Human T-cell leukemia virus type 1 (HTLV-1)-infected CD4(+) T cells and dendritic cells (DCs) are present in peripheral blood from HTLV-1 carriers. While T-cell infection requires cell-cell contact, ...DCs might be infected with cell-free virus, at least in vitro. However, a thorough comparison of the susceptibilities of the two cell types to HTLV-1 infection using cell-associated and cell-free viral sources has not been performed. We first determined that human primary monocyte-derived dendritic cells (MDDCs) were more susceptible to HTLV-1 infection than their autologous lymphocyte counterparts after contact with chronically infected cells. Next, a comparison of infection efficiency using nonconcentrated or concentrated supernatants from infected cells as well as purified viral biofilm was performed. Integrated provirus was found after exposure of MDDCs or primary lymphocytes to viral biofilm but not to a viral supernatant. Using a large series of primary cell samples (n = 21), we demonstrated a higher proviral load in MDDCs exposed to viral biofilm than in lymphocytes. This higher susceptibility is correlated to a higher expression of neuropilin-1 on MDDCs than on autologous activated T lymphocytes. Moreover, we show that MDDCs infected with viral biofilm can transmit the virus to lymphocytes. In conclusion, MDDCs are more susceptible to HTLV-1 infection than autologous lymphocytes in vitro, supporting a model in which DC infection might represent an important step during primo-infection in vivo.
HTLV-1 is able to infect several cell types, but viral DNA is mainly found in T lymphocytes in vivo. This supports a model in which T lymphocytes are the main target of infection. However, during the primo-infection of new individuals, incoming viruses might first encounter dendritic cells (DCs), the specialized immune cells responsible for the antiviral response of the host. HTLV-1 cell-free purified viruses can infect dendritic cells in vitro, while T-cell infection is restricted to cell-to-cell transmission. In order to understand the sequence of HTLV-1 dissemination, we undertook a direct comparison of the susceptibilities of the two cell types using cell-associated and cell-free viral sources. We report here that MDDCs are more susceptible to HTLV-1 infection than autologous lymphocytes in vitro and are able to efficiently transmit the virus to lymphocytes. Our results suggest that DCs may represent a true viral reservoir, as the first cell type to be infected in vivo.
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.
Human T cell leukemia virus type 1 (HTLV-1), the etiological agent of adult T cell leukemia/lymphoma (ATLL) and of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), was identified ...a few years before Human Immunodeficiency Virus (HIV). However, forty years later, our comprehension of HTLV-1 immune detection and the host immune responses to HTLV-1 is far more limited than for HIV. In addition to innate and adaptive immune responses that rely on specialized cells of the immune system, host cells may also express a range of antiviral factors that inhibit viral replication at different stages of the cycle, in a cell-autonomous manner. Multiple antiviral factors allowing such an intrinsic immunity have been primarily and extensively described in the context HIV infection. Here, we provide an overview of whether known HIV restriction factors might act on HTLV-1 replication. Interestingly, many of them do not exert any antiviral activity against HTLV-1, and we discuss viral replication cycle specificities that could account for these differences. Finally, we highlight future research directions that could help to identify antiviral factors specific to HTLV-1.
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of a neural chronic inflammation, called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and of a malignant ...lymphoproliferation, called the adult T-cell leukemia/lymphoma (ATLL). The mechanisms through which the HTLV-1 induces these diseases are still unclear, but they might rely on immune alterations. HAM/TSP is associated with an impaired production of pro-inflammatory cytokines and chemokines, such as IFN-γ, TNF-α, CXCL9, or CXCL10. ATLL is associated with high levels of IL-10 and TGF-β. These immunosuppressive cytokines could promote a protumoral micro-environment. Moreover, HTLV-1 infection impairs the IFN-I production and signaling, and favors the IL-2, IL-4, and IL-6 expression. This contributes both to immune escape and to infected cells proliferation. Here, we review the landscape of cytokine dysregulations induced by HTLV-1 infection and the role of these cytokines in the HTLV-1-associated diseases progression.
Human T cell leukemia virus type 1 (HTLV-1), the etiological agent of adult T-cell leukemia/lymphoma (ATLL) and the demyelinating neuroinflammatory disease known as HTLV-1-Associated ...Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), was the first human retrovirus to be discovered. T-cells, which represent the main reservoir for HTLV-1, have been the main focus of studies aimed at understanding viral transmission and disease progression. However, other cell types such as myeloid cells are also target of HTLV-1 infection and display functional alterations as a consequence. In this work, we review the current investigations that shed light on infection, transmission and functional alterations subsequent to HTLV-1 infection of the different myeloid cells types, and we highlight the lack of knowledge in this regard.
There is increasing evidence that viral infections are the source/origin of various types of encephalitis, encephalomyelitis, and other neurological and cognitive disorders. While the involvement of ...certain viruses, such as the Nipah virus and measles virus, is known, the mechanisms of neural invasion and the factors that trigger intense immune reactions are not fully understood. Based on recent publications, this review discusses the role of the immune response, interactions between viruses and glial cells, and cytokine mediators in the development of inflammatory diseases in the central nervous system. It also highlights the significant gaps in knowledge regarding these mechanisms.
Few years after HTLV-1 identification and isolation in humans, STLV-1, its simian counterpart, was discovered. It then became clear that STLV-1 is present almost in all simian species. Subsequent ...molecular epidemiology studies demonstrated that, apart from HTLV-1 subtype A, all human subtypes have a simian homolog. As HTLV-1, STLV-1 is the etiological agent of ATL, while no case of TSP/HAM has been described. Given its similarities with HTLV-1, STLV-1 represents a unique tool used for performing clinical studies, vaccine studies as well as basic science.
Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) are complex retroviruses mainly infecting CD4(+) T lymphocytes. In addition, antigen-presenting cells such ...as dendritic cells (DCs) are targeted in vivo by both viruses, although to a lesser extent. Interaction of HIV-1 with DCs plays a key role in viral dissemination from the mucosa to CD4(+) T lymphocytes present in lymphoid organs. While similar mechanisms may occur for HTLV-1 as well, most HTLV-1 data were obtained from T-cell studies, and little is known regarding the trafficking of this virus in DCs. We first compared the efficiency of cell-free versus cell-associated viral sources of both retroviruses at infecting DCs. We showed that both HIV-1 and HTLV-1 cell-free particles are poorly efficient at productively infecting DCs, except when DC-SIGN has been engaged. Furthermore, while SAMHD-1 accounts for restriction of cell-free HIV-1 infection, it is not involved in HTLV-1 restriction. In addition, cell-free viruses lead mainly to a nonproductive DC infection, leading to trans-infection of T-cells, a process important for HIV-1 spread but not for that of HTLV-1. Finally, we show that T-DC cell-to-cell transfer implies viral trafficking in vesicles that may both increase productive infection of DCs ("cis-infection") and allow viral escape from immune surveillance. Altogether, these observations allowed us to draw a model of HTLV-1 and HIV-1 trafficking in DCs.