Pathways of cell-cell transmission of HTLV-1

Abstract

The deltaretroviruses human T cell lymphotropic virus type 1 (HTLV-1) and human T cell lymphotropic virus type 2 (HTLV-2) have long been believed to differ from retroviruses in other genera by their mode of transmission. While other retroviruses were thought to primarily spread by producing cell-free particles that diffuse through extracellular fluids prior to binding to and infecting target cells, HTLV-1 and HTLV-2 were believed to transmit the virus solely by cell–cell interactions. This difference in transmission was believed to reflect the fact that, relative to other retroviruses, the cell-free virions produced by HTLV-infected cells are very poorly infectious. Since HTLV-1 and HTLV-2 are primarily found in T cells in the peripheral blood, spread of these viruses was believed to occur between infected and uninfected, T cells, although little was known about the cellular and viral proteins involved in this interaction. Recent studies have revealed that the method of transmission of HTLV is not unique: other retroviruses including human immunodeficiency virus (HIV) are also transmitted from cell-to-cell, and this method is dramatically more efficient than cell-free transmission. Moreover, cell–cell transmission of HTLV-1, as well as HIV, can occur following interactions between dendritic cells and T cells, as well as between T cells. Conversely, other studies have shown that cell-free HTLV-1 is not as poorly infectious as previously thought, since it is capable of infecting certain cell types. Here we summarize the recent insights about the mechanisms of cell–cell transmission of HTLV-1 and other retroviruses. We also review in vitro and in vivo studies of infection and discuss how these finding may relate to the spread of HTLV-1 between individuals.

Reducing the global burden of HTLV-1 infection: An agenda for research and action

“…This article presents the consensus views of taskforce members regarding unsolved or controversial issues that hamper further understanding of HTLV-1 and the development of new approaches for diagnosis, prevention and therapy. For additional information on the molecular mechanisms of pathogenesis, immunological aspects, epidemiology and currently available therapies for HTLV-1 infection, readers are referred to a number of excellent review articles (Bangham et al, 2015;Matsuoka and Jeang, 2007;Pique and Jones, 2012;Murphy, 2016;Gessain and Cassar, 2012;Kato and Akashi, 2015).…”

Sexual transmission of human T-cell lymphotropic virus type 1

“…Therefore, infl ammatory conditions might recruit lymphocytes to the genital tract, where they are infected with HTLV-1 particles. Conditions that are associated with an increased number of lymphocytes in cervicovaginal secretions and semen might result in an increased excretion of infected cells and a consequently higher risk of HTLV sexual transmission 81,82 . Zunt et al 61 detected cervical shedding of HTLV-1 deoxyribonucleic acid (DNA) in 68% of 63 HTLV-1-infected Peruvian sex workers.…”

Monoclonal antibody profiling of cell surface proteins associated with the viral biofilms on HTLV-1 transformed cells

“…Primary infection and consequent spreading of HTLV-1 in vivo are mediated by complex mechanisms of cell-to-cell viral transmission (Nejmeddine and Bangham, 2010;Pique and Jones, 2012) The pivotal role in this process belongs to HTLV-1 Tax protein, which coordinates cytoskeleton polarization, induces expression of adhesion molecule ICAM-1, promotes VS formation, and can potentially regulate VB-mediated viral transfer (Nejmeddine and Bangham, 2010). Interacting with transcription factors, signaling and transport molecules, cytoskeleton, PDZ proteins and other intracellular messengers, Tax induces global changes in the cellular transcriptome (reviewed in (Boxus et al, 2008)) as was demonstrated at the level of mRNA (Baba et al, 2008; The levels of CD antigen expression in Tax-positive cells relative to Tax-negative cells were calculated as the mean fluorescence intensity for PE in region 3 (R3) divided by the mean fluorescence intensity for PE in region 2 (R2); gating for regions R2 and R3 is shown in the left panel of Fig.…”

“…HIV causes the onset of a fatal immunodeficiency in all patients, while only 5% of individuals infected with HTLV-1 develop either adult T cell leukemia or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/ TSP). It has been shown that cell-to-cell transmission of these viruses mediated by so-called virological synapse (VS) is more efficient mechanisms of viral spread than infection with cell-free virus (Chen, 2012;Igakura et al, 2003;Jolly et al, 2004;Pique and Jones, 2012).…”