Human T-lymphotropic virus 1
|Human T-lymphotropic virus|
|Group:||Group VI (ssRNA-RT)|
|Species:||Simian T-lymphotropic virus|
Human T-lymphotropic virus
Human T-cell Lymphotropic virus or Human T-lymphotropic virus Type 1 (HTLV-I), also called the Adult T-cell lymphoma virus type 1 or (Adult T-cell leukemia lymphoma ATLL) a virus that has been implicated in several kinds of diseases including HTLV-I-associated myelopathy, Strongyloides stercoralis hyper-infection, and a virus cancer link for leukemia (see adult T-cell leukemia/lymphoma). Between one in twenty and one in twenty-five infected persons are thought to develop cancer as a result of the virus.
HTLV was discovered in 1977 in Japan. The virus was first isolated by Bernard Poiesz and Francis Ruscetti and their co-workers in the laboratory of Robert C. Gallo at the NCI. It was the first identified human retrovirus.
Clinical forms of ATLL
1- Acute : Leukemic picture, organomegally, high lactate dehydrogenase (LDH) and often hypercalcaemia. 2- Chronic: Lymphocytosis >4x109/L with ATLL cells, skin, lung, liver or node involvement, Normal calcium level, LDH normal or less that twice in upper normal limit. 3- Smouldering: Skin and/or lung infiltrating and no other organ involvement. Normal lymphocyte count(1-5% ATLL cells), normal calcium and LDH. 4- Lymphoma: Organomegally. less than 1% circulating leukemia cells, high LDH and possible hypercalcaemia.
Seven genotypes are recognised and about 20 million people are infected. 3-8 million are in Africa. The most widespread genotype is type A. Type B has only been isolated from Central Africa to date (2012). Type C is prevalent in Melanesia. Type D is also found in Central Africa.
The virus appears to have evolved from simian T-cell leukemia virus type 1.
Two subtypes are found in Japan: a transcontinental subgroup and a Japanese subgroup.
Signs and Symptoms
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Signs and symptoms of HTLV myelopathy
Signs and symptoms of HTLV myelopathy include:
- Motor and sensory changes in the extremities
- Spastic gait in combination with weakness of the lower limbs
- Bladder dysfunction(neurogenic bladder) and bladder cancer
Other neurologic findings that may be found in HTLV include:
HTLV-I infection in the United States appears to be about half as prevalent among IV drug users and about one-tenth as prevalent in the population at large as HIV infection. Although little serologic data exist, the prevalence of infection is thought to be highest among blacks living in the Southeast. A prevalence rate of 30% has been found among black intravenous drug users in New Jersey, and a rate of 49% has been found in a similar group in New Orleans. It is possible that prevalence of infection is increasing in this risk group.
HTLV-I infection in Australia is very high among the indigenous peoples of central and northern Australia, with a prevalence rate of 10-30%. It is also high among the Inuit of Northern Canada, in Japan, northeastern Iran, Peru, the Pacific coast of Colombia and Ecuador, the Caribbean, and in Africa.
Transmission of HTLV-I is believed to occur by sexual contact, from mother to child via breastfeeding, and through exposure to contaminated blood, either through blood transfusion or sharing of contaminated needles. The importance of the various routes of transmission is believed to vary geographically.
- In Japan, the geographic clustering of infections suggest that the virus is more dependent on mother-to-child transmission.
- In the Caribbean, the geographic distribution of the virus is more uniform, and it is more common among those with many sexual partners, indicating that sexual transmission is more common.
The term viral tropism refers to which cell types HTLV-I infects. Although HTLV-1 is primarily found in CD4+ T cells, other cell types in the peripheral blood of infected individuals have been found to contain HTLV-1, including CD8+ T cells, dendritic cells and B cells. HTLV-I entry is mediated through interaction of the surface unit of the virion envelope glycoprotein (SU) with its cellular receptor GLUT1, a glucose transporter, on target cells.
Individuals infected with HTLV-1 are at risk for opportunistic infections - diseases not caused by the virus itself, but by alterations in the host's immune functions.
HTLV-1, unlike the distantly related retrovirus HIV, has an immunostimulating effect which actually becomes immunosuppressive. The virus activates a subset of T-helper cells called Th1 cells. The result is a proliferation of Th1 cells and overproduction of Th1 related cytokines (mainly IFN-γ and TNF-α). Feedback mechanisms of these cytokines cause a suppression of the Th2 lymphocytes and a reduction of Th2 cytokine production (mainly IL-4, IL-5, IL-10 and IL-13). The end result is a reduction in the ability of the infected host to mount an adequate immune response to invading organisms that require a predominantly Th2 dependent response (these include parasitic infections and production of mucosal and humoral antibodies).
In the central Australian Aboriginal population, HTLV-1 is thought to be related to their extremely high rate of death from sepsis. It is also particularly associated with bronchiectasis, a chronic lung condition predisposing to recurrent pneumonia. It is also associated with chronic infected dermatitis, often superinfected with Staphylococcus aureus and a severe form of Strongyloides stercoralis infection called hyper-infestation which may lead to death from polymicrobial sepsis.
HTLV-1 is also associated with adult T cell leukemia/lymphoma and has been quite well studied in Japan. The time between infection and onset of cancer also varies geographically. It is believed to be about sixty years in Japan and less than forty years in the Caribbean. The cancer is thought to be due to the pro-oncogenic effect of viral DNA incorporated into host lymphocyte DNA. Chronic stimulation of the lymphocytes at the cytokine level may play a role in the development of the malignancy. The lymphoma ranges from a very indolent and slowly progressive type to a very aggressive and nearly uniformly lethal proliferative type.
Tropical spastic paraparesis
HTLV-1 is also associated with a progressive demyelinating upper motor neuron disease known as HAM/TSP, an abbreviation for HTLV-1 associated myelopathy/Tropical Spastic Paraparesis, characterized by sensory and motor deficits, particularly of the lower extremities, incontinence and impotence. Less than 2% of infected individuals develop HAM/TSP, but this will vary dramatically from one geographic location to another.
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Treatment of opportunistic infections varies depending on the type of disease and ranges from careful observation to aggressive chemotherapy and antiretroviral agents. Adult T cell lymphoma is a common complication of HLTV infection and requires aggressive chemotherapy, typically R-CHOP. Other treatments for ATL in HLTV infected patients include interferon alpha, zidovudine with interferon alpha and CHOP with arsenic trioxide. Treatments for HLTV myelopathy are even more limited and focus mainly on symptomatic therapy. Therapies studied include corticosteroids, plasmapheresis, cyclophosphamide, and interferon, which may produce a temporary symptomatic improvement in myelopathy symptoms.
Valproic acid has been studied to determine if it might slow the progression of HLTV disease by reducing viral load. Although in one human study it was effective in reducing viral load, there did not appear to be a clinical benefit. Recently however, a study of valproic acid combined with zidovudine showed a major decrease in the viral load of baboons infected with HLTV-1. It is important to monitor HLTV patients for opportunistic infections such as cytomegalovirus, histoplasmosis, scabies, pneumocystis pneumonia, and staphylococcal infections. HIV testing should also be performed, as some patients may be co-infected with both viruses.
Allogenic bone marrow transplantation has been investigated in the treatment of HLTV-1 disease with varied results. One case report describes an HLTV-1 infected woman who developed chronic refractory eczema, corneal injury and adult T cell leukemia. She was subsequently treated with allogenic stem cell transplantion and had complete resolution of symptoms. One year post-transplant, she has had no recurrence of any symptoms, and furthermore has had a decrease in her proviral load.
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- International Retrovirology Association
- Human T-lymphotropic virus 1 at the US National Library of Medicine Medical Subject Headings (MeSH)