Human t-cell lymphotropic virus

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

HTLV; human T-cell leukemia virus

History
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Gallo, 1980

Definition
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HTLV1 a retrovirus is the cause of T-cell leukemia, which occurs exclusively in adulthood. The virus also causes neurological diseases. Reservoir are CD4-T lymphocytes.

Its closest relative HTLV2 was isolated from a patient with hairy cell leukemia in 1982.

Pathogen
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Human T-cell lymphotropic virus 1 and 2 (and in question also 3 and 4), family: Retroviridae, subfamily: Orthoretrovirinae, genus: Deltaretrovirus.

In patients, the HTL virus integrates itself into the genome of T lymphocytes (CD4+). During infection, the virus probably integrates into the genome of many T-lymphocytes at different locations in the DNA (so-called polyclonal distribution). During the latency phase of the infection (20-30 years), however, certain lymphocyte clones are then selected, so that in the end mostly only T-cells are found, in which the virus is either always inserted at the same place (monoclonal distribution) or only at very few different places in the DNA (oligoclonal).

However, the insertion sites are always different for each patient. From this it can be concluded that the insertion site in the DNA plays no role in the malignant degeneration of the affected cells. Chromosomal abnormalities are frequently observed in HTLV-infected lymphocytes, especially in acute forms of leukemia.

HTLV infection triggers massive cell proliferation, with the virally encoded "tax protein" having an activating effect on cellular promoters. These proliferating clones then form the basis for the developing malignant T-cell clones.

Occurrence/Epidemiology
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Occurrence: Central and South America, Caribbean, Japan, tropical Africa, USA, Middle East.

Transmission: connatal, blood transfusions, breast milk, intimate contacts, contaminated cannula.

HTLV 2 is found in western countries (especially the USA) mainly in drug addicts. There is also a high prevalence in isolated indigenous tribes. The virus is practically non-existent in Europe.

In Japan, the number of people infected with HTLV-1 is around 1.0 million. Seropositivity for HTLV-specific antibodies varies between 1% and 35% in endemic areas, depending on the region. In Europe, HTLV-infected persons are rarely found (risk groups, e.g. drug users).

Etiology
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Viruses can be detected in the mononuclear cells of peripheral blood, infiltrates and nerve cells that cause chronic inflammation. It is disputed whether autoimmune processes play a role in the pathogenesis.

The transmission of the virus can occur in several ways:

  • Vertically: from HTLV infected mothers transplacentally to the infant
  • Sexual intercourse: apparently the transmission from man to woman plays a decisive role
  • Blood transfusions: Blood plasma is apparently not infectious because HTLV is highly cellassified.

Clinical picture
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HTLV-1, more rarely HTLV-2 induced diseases:

  • Malignant lymphoma(adult T cell lymphoma/leukemia (HTLV+). Acute leukemia develops 20-30 years after primary infection. Patients have >5% abnormal lymphocytes and hypercalcemia. The mean survival time is 6 months.
  • Spinal myelodegeneration (HTLV-1 myelopathy) with accompanying immunodeficiency
  • Opportunistic infections such as scabies, Pneumocystis jiroveci pneumonia and strongyloidiasis.
  • HTLV-1 associated infective dermatitis (HTLV-1 associated infective dermatitis): rare, severe, exudative eczematous lesions of the head, axillae and groin. Predominantly multiple disseminated or confluent small papules are present, up to generalized infestation. The skin changes precede the myelopathy. Probably an allergic remote reaction to superinfecting bacteria is present ( Id reaction).
  • Myelopathy: usually begins in the 5th decade of life. Incubation period: 12 months. Slowly progressive spastic paraparesis, increased muscle tone, hyperreflexia, lumbar back pain, urge to urinate with incontinence and sexual impotence, weakness of the proximal leg muscles. In some patients there are also paraventricular demyelination foci of the brain.
  • Autoimmune syndromes (accompanying) such as uveitis, arthritis and Sjögren's syndrome.

There are mostly healthy HTLV-I carriers.

Diagnosis
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Clinical symptoms

Lymphocytosis, activated lymphocytes, increased CD4/CD8 ratio.

Polyclonal antibody production.

Serum antibodies (ELISA, immunoblot).

Direct virus detection in blood and tissue by PCR.

Therapy
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Symptomatic. Possibly treatment of opportunistic infections. A vaccine is still not available. Chemotherapeutics are also not effective.

Literature
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  1. Marchetti MA et al (2015) Cutaneous manifestations of human T-cell lymphotrophic virus type-1-associated adult T-cell leukemia/lymphoma: a single-center, retrospective study. J Am Acad Dermatol 72:293-301
  2. Murata K, Yamada Y (2007) The state of the art in the pathogenesis of ATL and new potential targets associated with HTLV-1 and ATL. Int Rev Immunol 26: 249-268
  3. Taylor G (2007) Molecular aspects of HTLV-I infection and adult T-cell leukaemia/lymphoma. J Clin Pathol 60: 1392-1396
  4. Torres-Cabala CA et al (2015) HTLV-1-associated infective dermatitis demonstrates low frequency of FOXP3-positive T-regulatory lymphocytes. J Dermatol Sci 77:150-155
  5. Tsukasaki K et al (2014) Human T-cell lymphotropic virus type I-associated adult T-cell leukemia-lymphoma: new directions in clinical research. Clin Cancer Res 20: 5217-5225
  6. Yoshida N et al (2015) Incidence of adult T-cell leukemia/lymphoma in nonendemic areas. Curr Treat Options Oncol 16:321

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

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Last updated on: 29.10.2020