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HTLV-1 Associated Neurological Disorders

Authors:
Muhammad Yasir Khan at King Abdulaziz University
Muhammad Yasir Khan
Ishaq Khan at Texas A&M University System Health Science Center
Ishaq Khan
Muhammad Farman at King Abdulaziz University
Muhammad Farman
Saleh Alkarim at King Abdulaziz University
Saleh Alkarim
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Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus which is endemic to certain regions of the world and infects around 10-20 million people. HTLV-1 is the etiologic agent of Adult T cell leukemia/lymphoma and HTLV-1 associated neurological disorders including mainly HTLV-1 associated myelopathy/Tropical spastic paraparesis. The involvement of the central nervous diseases occurs among: HTLV-1 infected patients from endemic areas, HIV positive individuals and drug users. The ability of HTLV-1 to cause associated neuropathies starts with the virus crossing the blood brain barrier (BBB), then entering and infecting the cells of the central nervous system. As a consequence, to the viral attack, HTLV-1 infected lymphocytes produce pro-inflammatory cytokines like tumor necrosis factor alpha, Interleukin 1 beta and interleukin 6 which further disrupts the BBB. Different serological tests have been used in the diagnosis of HTLV-1. These include: ELISA, Western Blotting (WB), Immunofluorescence, Particle Agglutination and Polymerase Chain Reaction which is used as a confirmatory test. Danazol, pentoxifylline, azathioprine and vitamin C have been used in the treatment of the HTLV-1 associated neurological disorders. Other antiviral drugs (lamivudine, zidovudine), monoclonal antibodies (Daclizumab) and therapeutic agents (valporic acid, interferons) have also been evaluated. No known drug, so far, has been shown to be efficacious. The aim of this review is to present the complexities of HTLV-1 associated neurological disorders and their current ongoing treatment. In addition to discussing future possible therapeutic strategies, by targeting HTVL-1 viral components and gene/s products, for the treatment of those neurological conditions.
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Journal Name:Current Topics in Medicinal Chemistry
HTLV-1 Associated Neurological Disorders
Muhammad Yasir Khan, Ishaq Nasib Khan, Muhammad Farman, Saleh Al Karim, Ishtiaq
Qadri, Muhammad Amjad Kamal, Khalid Al Ghamdi, Steve Harakeh.
Volume 17 , Issue 12 , 2017 DOI : 10.2174/1568026616666161222141318
Abstract
Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus which is endemic
to certain regions of the world and infects around 10-20 million people. HTLV-1 is the
etiologic agent of Adult T cell leukemia/lymphoma and HTLV-1 associated
neurological disorders including mainly HTLV-1 associated myelopathy/Tropical
spastic paraparesis. The involvement of the central nervous diseases occurs among:
HTLV-1 infected patients from endemic areas, HIV positive individuals and drug
users. The ability of HTLV-1 to cause associated neuropathies starts with the virus
crossing the blood brain barrier (BBB), then entering and infecting the cells of the
central nervous system. As a consequence, to the viral attack, HTLV-1 infected
lymphocytes produce pro-inflammatory cytokines like tumor necrosis factor alpha,
Interleukin 1 beta and interleukin 6 which further disrupts the BBB. Different
serological tests have been used in the diagnosis of HTLV-1. These include: ELISA,
Western Blotting (WB), Immunofluorescence, Particle Agglutination and Polymerase
Chain Reaction which is used as a confirmatory test. Danazol, pentoxifylline,
azathioprine and vitamin C have been used in the treatment of the HTLV-1
associated neurological disorders. Other antiviral drugs (lamivudine, zidovudine),
monoclonal antibodies (Daclizumab) and therapeutic agents (valporic acid,
interferons) have also been evaluated. No known drug, so far, has been shown to be
efficacious. The aim of this review is to present the complexities of HTLV-1
associated neurological disorders and their current ongoing treatment. In addition to
discussing future possible therapeutic strategies, by targeting HTVL-1 viral
components and gene/s products, for the treatment of those neurological conditions
Keywords: HTLV-1, Reteroviradae, Antiviral drugs, Neurological disorders, Blood brain
barrier, Pathogenesis, New drugs discovery
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... The data reported above not only open new scenarios for effective and specific anti-HTLV-1 vaccine formulations, but can also provide a potential mechanistic link between HTLV-1 infection and related disorders including lymphomas and leukemias, respiratory disorders, fibromyalgia, rheumatoid arthritis, arthritis, tuberculosis, kidney and bladder infections, dermatophytosis, community acquired pneumonia, strongyloides hyperinfection syndrome, liver cancer, lymphoma, cervical cancer, and neurological disorders [1,2]. ...
... Identified as described under Methods and in text.2 Detailed methods and discussion and in text. ...
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... In 1980 based on a Japanese report from a patient with T cell malignancy, the Human T cell leukemia virus (HTLV-1) was first described and belonged to the retroviridae family (1,2). It has been estimated that worldwide HTLV-1 infection is around 10-20 million people (3,4). ...
... HTLV-1causes two life-threatening diseases, adult T cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/ tropical spastic paraparesis (HAM/TSP) in only 3-5% of infected subjects (6,7). Thus the main proportion of HTLV-1infected individuals remains healthy carriers (2,8). It is not completely understood why only a small percentage develop into the nominated associated diseases after a long time of infection (1). ...
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Full-text available
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