HTLV‐1

Charles RM Bangham, Imperial College Faculty of Medicine, London, UK

Published online: December 2011

DOI: 10.1002/9780470015902.a0023613

Human T lymphotropic virus Type 1 (HTLV-1) was the first human retrovirus discovered. Like the related virus human immunodeficiency virus Type-1 (HIV-1), HTLV-1 persists lifelong in the host. HIV-1 causes disease in over 99% of untreated infected people, whereas HTLV-1 causes disease in only 2–8%: either a fatal leukaemia or lymphoma, or a disabling chronic inflammatory disease of the nervous system that causes paralysis of the legs. There is no satisfactory treatment for the malignant or inflammatory diseases, and no vaccine. HTLV-1 is thought to have existed in the human population for over 50 thousand years; it is widely but unevenly distributed in the tropics and in some subtropical areas. A highly dynamic equilibrium is established in each infected person between persistent HTLV-1 replication and the host immune response. The increasing understanding of this equilibrium has led to discoveries and conclusions of wide significance for virology, immunology and persistent infections.

Key Concepts:

  • Viral load and risk of HTLV-1-associated diseases are determined by the efficiency of the host's cell-mediated immune response.
  • Immunological efficiency is determined by host genetic polymorphisms – chiefly HLA – and by targeting critical weak points in the pathogen's life cycle.
  • An immunodominant antigen is not necessarily the antigen recognised by the protective host immune response.
  • Attributes of T cells such as phenotype, frequency and function do not correlate with their efficiency in protecting against a pathogen in a persistent infection at equilibrium.
  • Viruses that target mobile cells such as leukocytes can use the mobility of the host cell to spread within and between hosts: they do not need to release large numbers of cell-free virus particles.
  • Some viruses, such as HTLV-1, can spread from one cell to another by an active, triggered process that involves formation of a specialised cell-to-cell contact called a virological synapse.

Keywords: retrovirus; HTLV-1; cytotoxic T lymphocyte (CTL); virological synapse (VS); persistent infection; tropical spastic paraparesis; CTL efficiency; leukaemia; viral oncogenesis

Figure 1. Origin, spread, and prevalence of HTLV-1. Origin and spread hypothesis based on phylogenetic and anthropological data. PTLV (primate T-lymphotropic virus) originated in African primates and migrated to Asia where it evolved into STLV-1. This early STLV-1 lineage spread to India, Japan, Indonesia and back to Africa (arrows 1). It crossed the simian–human barrier in Indonesian human beings who migrated to Melanesia, resulting in the HTLV-1c subtype (arrows 2). In Africa, STLV-1 evolved through several interspecies transmissions into HTLV-1a, HTLV-1b, HTLV-1d, HTLV-1e, and HTLV-1f (arrows 3). Because of the slave trade and increased mobility, HTLV-1a was introduced in the New World, Japan, the middle east and north Africa (arrows 4). Colours indicate current prevalence estimates based on population surveys and on studies in pregnant women and blood donors. In some countries, HTLV-1 infection is limited to certain population groups or areas. (Reproduced with permission from Figure 4 in Verdonck et al., 2007a, 2007b.)
Figure 2. Structure and coding potential of plus- and minus-strand HTLV-1 mRNAs. (Reproduced with permission from Figure 1a in Rende et al., 2011. © The American Society of Hematology.)
Figure 3. The virological synapse (VS). HTLV-1 Gag protein (red), and the host cell protein talin (green), which associates with the adhesion molecule LFA-1, accumulate at the cell–cell interface at the VS. (a) Lateral view of conjugate formed between two lymphocytes from an HTLV-1-infected person. (b) z-Axis image reconstruction of cell–cell interface. (Reproduced with permission from Figure 2b and c in Igakura et al., 2003.)
Figure 4. Illustration of possible routes of HTLV-1 spread between cells in vivo. (a) cell-to-cell transmission via intercellular synaptic cleft surrounded by a tight cell–cell contact between the donor and recipient cell, 1. Cell-free particles can be internalised by dendritic cells and are then transferred to lymphocyte only by cell-to-cell contact, 2. Virus particles can be retained on the cell surface in a biofilm-like structure before lateral transfer to the recipient outside the cell–cell contact region, 3. (b) In an isolated HTLV-1-infected lymphocyte, the viral proteins are not polarised. (Reproduced with permission from Figure 3 in Nejmeddine and Bangham, 2010.)
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 Further Reading
    book Sompayrac LM (2002) How Pathogenic Viruses Work. Sudbury, MA: Jones and Bartlett Publishers, Inc.
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Related Sub-Topics:

Infection | Inflammation | Acquired (Adaptive) Immunity | Innate Immunity | Tumour Immunology | Virus Diseases | Viruses Infecting Humans | RNA Viruses
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Article Title: HTLV‐1
 
How to Cite close
Bangham, Charles RM(Dec 2011) HTLV‐1. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023613]