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Neuraminidase enhances the initial steps of human T-cell leukemia virus type 1 replication
Authors:Masakazu Tanaka  Binlian Sun  Kenta Tezuka  Jun-ichi Fujisawa  Yuetsu Tanaka  Hiroo Hoshino  Masanao Miwa
Institution:1. Graduate School of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan;2. Department of Microbiology, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan;3. Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan;4. Department of Infectious Diseases and Immunology, Okinawa-Asia Research Center of Medical Science, Faculty of Medicine, University of the Ryukyus, Uehara 207, Okinawa 903-0215, Japan;5. Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan;1. Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Disease, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, PR China;2. Department of Intractable Diseases, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan;1. Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan;2. Department of Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan;3. Musculoskeletal Oncology Service, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan;4. Department of Orthopaedic Surgery, Osaka National Hospital, Kinki-Block Comprehensive Cancer Center, 2-1-14 Hoenzaka, Chuo-ku, Osaka 540-0006, Japan;1. Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan;2. Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan;3. Department of Surgery, Asahi General Hospital, Chiba, Japan;4. Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan;5. Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki, Japan;6. Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo, Japan;7. Department of Internal Medicine, JA Kochi Hospital, Kochi, Japan;8. Life Science Center of Tsukuba Advanced Research Alliance (TARA), The University of Tsukuba, Tsukuba, Ibaraki, Japan;3. School of Systems Biology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia 20110,;4. Department of Microbiology, Immunology, and Tropical Medicine and George Washington University Medical Center, Washington, D. C. 20037;12. Center for Microscopy and Image Analysis, George Washington University Medical Center, Washington, D. C. 20037,;9. Equipe Oncogenèse Rétrovirale, Equipe labelisée “Ligue Nationale Contre le Cancer,” International Center for Research in Infectiology, INSERM U1111-CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon 1, Lyon 69364 Cedex 07, France,;5. Unité d''Epidémiologie et Physiopathologie des Virus Oncogènes, Département de Virologie, Institut Pasteur, F-75015 Paris, France,;6. CNRS, UMR3569, F-75015 Paris, France, and;8. Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology Research, Drexel University College of Medicine, Doylestown, Pennsylvania 18902;3. Division of Cancer Glycosylation Research, Tohoku Pharmaceutical University, Sendai, 981-8558;5. Division of Glyco-Signal Research, Tohoku Pharmaceutical University, Sendai, 981-8558;6. Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, 981-8558;12. Bioscience and Biotechnology Center, Nagoya University, Nagoya, 464-8601;8. Miyagi Cancer Center Research Institute, Natori, 981-1293;4. Division of Cancer Molecular Biology, Graduate School of Medicine, Tohoku University, Sendai, 980-8575, Japan
Abstract:Human T-cell leukemia virus type 1 (HTLV-1) infection is involved in the development of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. A high HTLV-1 proviral load in circulating lymphocytes of HTLV-1 carriers is a risk factor for HTLV-1-related diseases. The virus–cell interaction is linked to viral tropism and pathogenesis. Characterization of the factors that affect HTLV-1 infection is important for preventing HTLV-1 infection. HTLV-1 virions are believed to be weakly infectious under cell culture conditions; however, we found that the treatment of HTLV-1 virions with microbial neuraminidase, an enzyme catalyzing the removal of sialic acid residues from various glycoconjugates, enhanced the number of proviral DNAs in infected cells in a dose-dependent manner. Neuraminidase treatment of virions, but not target cells, enhanced viral binding and entry into cells and viral infectivity; treatment of target cells prior to infection had no effect. Moreover, the number of HTLV-1-mediated syncytia was higher in the presence of neuraminidase. Our results suggest a possible contribution of microbial agents carrying neuraminidase activity to HTLV-1 pathogenesis.
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