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      HTLV-1, the Other Pathogenic Yet Neglected Human Retrovirus: From Transmission to Therapeutic Treatment

      review-article
      1 , 2 , 1 , 2 , 1 , 2 , *
      Viruses
      MDPI
      HTLV-1, HIV-1, viral transmission, ATLL, TSP/HAM, treatments

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          Abstract

          Going back to their discovery in the early 1980s, both the Human T-cell Leukemia virus type-1 (HTLV-1) and the Human Immunodeficiency Virus type-1 (HIV-1) greatly fascinated the virology scene, not only because they were the first human retroviruses discovered, but also because they were associated with fatal diseases in the human population. In almost four decades of scientific research, both viruses have had different fates, HTLV-1 being often upstaged by HIV-1. However, although being very close in terms of genome organization, cellular tropism, and viral replication, HIV-1 and HTLV-1 are not completely commutable in terms of treatment, especially because of the opposite fate of the cells they infect: death versus immortalization, respectively. Nowadays, the antiretroviral therapies developed to treat HIV-1 infected individuals and to limit HIV-1 spread among the human population have a poor or no effect on HTLV-1 infected individuals, and thus, do not prevent the development of HTLV-1-associated diseases, which still lack highly efficient treatments. The present review mainly focuses on the course of HTLV-1 infection, from the initial infection of the host to diseases development and associated treatments, but also investigates HIV-1/HTLV-1 co-infection events and their impact on diseases development.

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          Most cited references182

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          Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells.

          Evidence suggests that CD8+ T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1 alpha, and MIP-1 beta were identified as the major HIV-SF produced by CD8+ T cells. Two active proteins purified from the culture supernatant of an immortalized CD8+ T cell clone revealed sequence identity with human RANTES and MIP-1 alpha. RANTES, MIP-1 alpha, and MIP-1 beta were released by both immortalized and primary CD8+ T cells. HIV-SF activity produced by these cells was completely blocked by a combination of neutralizing antibodies against RANTES, MIP-1 alpha, and MIP-1 beta. Recombinant human RANTES, MIP-1 alpha, and MIP-1 beta induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). These data may have relevance for the prevention and therapy of AIDS.
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            Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation.

            It has been 30 years since a 'new' leukaemia termed adult T-cell leukaemia (ATL) was described in Japan, and more than 25 years since the isolation of the retrovirus, human T-cell leukaemia virus type 1 (HTLV-1), that causes this disease. We discuss HTLV-1 infectivity and how the HTLV-1 Tax oncoprotein initiates transformation by creating a cellular environment favouring aneuploidy and clastogenic DNA damage. We also explore the contribution of a newly discovered protein and RNA on the HTLV-1 minus strand, HTLV-1 basic leucine zipper factor (HBZ), to the maintenance of virus-induced leukaemia.
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              Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease.

              A retrovirus (ATLV) was unequivocally demonstrated in human adult T-cell leukemia (ATL) cell lines by density (1.152-1.155 g/cm3) in a sucrose gradient, reverse transcriptase activity insensitive to actinomycin D, RNA labeled with [3H]uridine, and specific proteins with molecular weights of 11,000, 14,000, 17,000, 24,000, and 45,000. Furthermore, cDNA prepared by endogenous reaction with detergent-treated virions hybridized to 35S RNA containing poly(A), which was inducible by IdUrd treatment of a T-cell line derived from leukemic cells of the ATL, and the integrated form of ATLV proviral DNA was detected in T-cell lines derived from ATL. The ATLV proviral DNA was also detected in fresh peripheral lymphocytes from all five patients with ATL tested so far but not in those from healthy adults. On the other hand, ATLV protein of Mr 42,000 was found to be at least one of the ATL-associated antigen(s) that were previously detected in ATL-leukemic cells by all sera from patients with ATL. These findings on the close association of ATLV protein and proviral DNA with ATL are direct evidence for the possible involvement of the retrovirus ATLV in leukemogenesis of human ATL.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                21 December 2017
                January 2018
                : 10
                : 1
                : 1
                Affiliations
                [1 ]International Center for Research in Infectiology, Retroviral Oncogenesis Laboratory, INSERM U1111—Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, F-69007 Lyon, France; nicolas.futsch@ 123456ens-lyon.fr (N.F.); renaud.mahieux@ 123456ens-lyon.fr (R.M.)
                [2 ]Equipe labellisée “Ligue Nationale Contre le Cancer”, France
                Author notes
                Article
                viruses-10-00001
                10.3390/v10010001
                5795414
                29267225
                e087dedb-df3b-4caa-bb92-311ff78f1231
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 November 2017
                : 18 December 2017
                Categories
                Review

                Microbiology & Virology
                htlv-1,hiv-1,viral transmission,atll,tsp/ham,treatments
                Microbiology & Virology
                htlv-1, hiv-1, viral transmission, atll, tsp/ham, treatments

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