Faculty Profiles - TAKASHIMA Hiroshi

Hikiami R, Yamashita H, Koita N, Jingami N, Sawamoto N, Furukawa K, Kawai H, Terashima T, Oka N, Hashiguchi A, Takashima H, Urushitani M, Takahashi R. . Charcot-Marie-Tooth disease type 2A with an autosomal-recessive inheritance: the first report of an adult-onset disease. . J Hum Genet63 ( 1 ) 89 - 92 2018.1Charcot-Marie-Tooth disease type 2A with an autosomal-recessive inheritance: the first report of an adult-onset disease.Reviewed

Hikiami Ryota, Yamashita Hirofumi, Koita Natsuko, Jingami Naoto, Sawamoto Nobukatsu, Furukawa Kaoru, Kawai Hiromichi, Terashima Tomoya, Oka Nobuyuki, Hashiguchi Akihiro, Takashima Hiroshi, Urushitani Makoto, Takahashi Ryosuke . 常染色体劣性遺伝を伴うCharcot-Marie-Tooth病2A型　成人発症による初報告(Charcot-Marie-Tooth disease type 2A with an autosomal-recessive inheritance: the first report of an adult-onset disease) . Journal of Human Genetics63 ( 1 ) 89 - 92 2018.1常染色体劣性遺伝を伴うCharcot-Marie-Tooth病2A型　成人発症による初報告(Charcot-Marie-Tooth disease type 2A with an autosomal-recessive inheritance: the first report of an adult-onset disease)Reviewed International journal

Language：English Publisher：Nature Publishing Group

中年期になってCharcot-Marie-Tooth病2A型(CMT2A)を発症した、日本人姉妹2例を報告した。症例1は3人姉妹の三女で、41歳時に両足裏に感覚麻痺を呈し、つま先歩きが困難になった。症状は徐々に悪化し、5年以内に杖歩行となり、52歳時の神経学的検査により、遠位下肢筋力低下と萎縮および反射消失が認められた。症例2は姉妹の長女で、42歳時に緩徐進行性の歩行困難を来たし、その後、両足裏の感覚麻痺が認められた。65歳時に車椅子生活となり、神経学的検査により、遠位下肢筋力低下、反射消失および感覚消失が認められた。なお、姉妹の次女に関しては、62歳時の神経学的検査では異常はみられなかったが、症例1および2では、MFN2遺伝子の膜貫通ドメインに対応するホモ接合性ミスセンス変異c.1894C>T、p.T632Wが同定された。一方、神経学的検査で正常であった次女では、これら変異はヘテロ接合性であったことから、遺伝子型と表現型の共分離が示唆された。MRIにより、症例1と2には脊髄、特に胸髄おける萎縮と、頭頂葉および小脳の軽度な萎縮が認められ、腓腹神経の電子顕微鏡観察により、円形および膨潤したミトコンドリアのクラスターの存在が明らかにされた。

Kazushi Minami, Shinichi Takahashi, Yoshihiro Nihei, Koichi Oki, Shigeaki Suzuki, Daisuke Ito, Hiroshi Takashima, Norihiro Suzuki . The first report of a japanese case of seipinopathy with a BSCL2 N88S mutation . Internal Medicine57 ( 4 ) 613 - 615 2018Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Society of Internal Medicine

Seipinopathy is an autosomal dominant neurodegenerative disease caused by mutations of the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) gene. We report the first Japanese case of seipinopathy with a heterozygous mutation of p.N88S in the BSCL2 gene. The patient showed bilateral hyperreflexia of the biceps, triceps, brachioradialis, and knee, as well as the pes cavus and distal dominant weakness and atrophy of both arms and legs, suggesting the involvement of both upper and lower motor neurons. Mutations of the BSCL2 gene have been known to cause motor neuron degeneration through endoplasmic reticulum stress. Seipinopathy should be considered in patients with symptoms mimicking amyotrophic lateral sclerosis.

DOI： 10.2169/internalmedicine.8765-16

Yamaguchi M, Takashima H . Drosophila Charcot-Marie-Tooth Disease Models. . Advances in experimental medicine and biology1076 97 - 117 2018Reviewed International journal

Shimizu Chisato, Kasahara Hiroo, Furuta Natsumi, Shibata Makoto, Nagashima Kazuaki, Hashiguchi Akihiro, Takashima Hiroshi, Ikeda Yoshio . Charcot-Marie-Tooth disease showing transient central nervous system lesions after a large amount of alcohol intake: A case report . Rinsho Shinkeigaku58 ( 8 ) 479 - 484 2018Reviewed

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Societas Neurologica Japonica

A 23-year-old man experienced numbness in the perioral region and right arm, and right leg weakness on the second day after drinking a large amount of alcohol during foreign travel. His symptoms disappeared but then reappeared repetitively. Cerebral MRI performed on the third day after onset showed multiple white matter lesions; however, these lesions disappeared 26 days after onset. Neurological examination and nerve conduction studies revealed demyelinating polyneuropathy. Genetic testing for Charcot-Marie-Tooth disease, X-linked dominant 1 (CMTX1) due to GJB1 mutation was conducted based on the symptoms of transient central nervous system lesions and polyneuropathy exhibited by the patient and his mother. As a result, a c.530T>C (p.V177A) substitution in exon 2 of GJB1 was identified. CMTX1 patients should be advised to avoid excessive drinking because this could induce central nervous system lesions.

DOI： 10.5692/clinicalneurol.cn-001130

Takemaru Makoto, Shimoe Yutaka, Sato Kota, Hashiguchi Akihiro, Takashima Hiroshi, Kuriyama Masaru . Transient, recurrent, white matter lesions in X-linked Charcot-Marie-Tooth disease with heterozygote mutation of GJB1 gene: case report of a female patient . Rinsho Shinkeigaku58 ( 5 ) 302 - 307 2018Reviewed

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Societas Neurologica Japonica

A 32-year-old woman showed transient central type facial nerve palsy and bulbar symptoms. Brain MRI revealed high intensity signals in the cerebral white matter, splenium of corpus callosum, and posterior limb of internal capsule. Two elder brothers of the patient had distal dominant peripheral neuropathies in four limbs. In this family, the point mutation of GJB1 gene, encoding connexin 32, was revealed and X-linked Charcot-Marie-Tooth disease (CMTX1) was diagnosed. The presented case was a heterozygote of this mutation. She showed severe transient central nervous system (CNS) symptoms and subclinical demyelinating peripheral neuropathy. The CNS symptoms and alterations of brain images were very similar among three siblings. There are many reports on male patients with CMTX1 who show associated CN symptoms, but female patients are very rare. There has been no previous report of a CMTX1 patient similar to the patient presented here. The trigger factors have been recognized at the onset of transient CN symptoms in these cases. The prevention of these factors is important for the management of such patients.

DOI： 10.5692/clinicalneurol.cn-001138

髙嶋博 . 自己免疫性脳症の臨床症候と治療の実際　―ヒステリーとの鑑別― . 神経治療学35 ( 6 ) S105 - S105 2018

Hamada Kyosuke, Takei Ran, Sakiyama Yusuke, Moriyama Hiroto, Hashiguchi Akihiro, Takashima Hiroshi . A case of chronic progressive neuro-Behçet disease with extensive cerebral atrophy and elevated CSF IL-6 activity treated with infliximab . Rinsho Shinkeigaku58 ( 1 ) 30 - 34 2018Reviewed

Language：Japanese Publisher：Societas Neurologica Japonica

A 43-year-old man without a previous episode of uveitis presented with slowly progressive neurological symptoms that appeared within the past year such as dysarthria, ataxic gait, and behavioral changes. Brain MRI findings showed atrophic lesions in the brainstem and cerebellum. Because these clinical symptoms and abnormal MRI findings indicated spinocerebellar degeneration as the initial diagnosis, he was admitted to our hospital. On admission, we noticed that he had non-neurological manifestations of Behçet disease, such as stomatitis, genital ulcers, and folliculitis. HLA-B51 was positive. He also showed pleocytosis (29 cells/mm3, predominantly mononuclear cells) and elevated cerebrospinal fluid (CSF) IL-6 levels (213 pg/ml), hence he was diagnosed with chronic progressive neuro-Behçet disease (CPNBD). The therapeutic effect of a high-dose intravenous methylprednisolone pulse (1,000 mg/day for 3 days) and methotrexate (maximum dosage, 16 mg/week) was poor against both neurological symptoms and CSF findings. Intravenous infliximab therapy (5 mg/kg, 2 weeks) dramatically decreased CSF IL-6 levels (13 pg/ml) but clinical symptoms remained unchanged. MRI findings of extensive cerebral atrophy and increased CSF IL-6 levels at the pretreatment time point reflected irreversible neurological involvement in CPNBD. For cases with progressive psychiatric symptoms and cerebellar ataxia in the early stage of the disease, skin manifestations should be examined immediately, CSF IL-6 levels measured, and immunosuppressive therapy initiated before CPNBD progresses to brainstem atrophy.

DOI： 10.5692/clinicalneurol.cn-001086

Sakiyama Yusuke, Takashima Hiroshi . Review/Advances in Neurological Therapeutics (2017). Spinocerebellar degeneration . Neurological Therapeutics35 ( 5 ) 605 - 608 2018Reviewed

Language：Japanese Publisher：Japanese Society of Neurological Therapeutics

We reviewed the recent advances in therapeutics of spinocerebellar degeneration (SCD) that were published in 2017. This article introduces the outline of therapies with antisense oligonucleotide, docosahexaenoic acid, mesenchymal stem cells, acetyl–DL–leucine, and rehabilitation using wearable devices and virtual reality. We expect that these treatments will contribute to patients with SCD.

DOI： 10.15082/jsnt.35.5_605

Kodama Kento, Takashima Hiroshi, Sakiyama Yusuke, Kozako Takuya, Takei Ran, Nakamura Tomonori, Hashiguchi Akihiro, Michizono Kumiko, Matsuura Eiji, Nakane Shunya . A case of systemic anhidrosis with anti-ganglionic acetylcholine receptor antibody . Nihon Naika Gakkai Zasshi107 ( 1 ) 95 - 102 2018Reviewed

Mineki Saito, Hiroe Sejima, Tadasuke Naito, Hiroshi Ushirogawa, Toshio Matsuzaki, Eiji Matsuura, Yuetsu Tanaka, Tatsufumi Nakamura, Hiroshi Takashima . The CC chemokine ligand (CCL) 1, upregulated by the viral transactivator Tax, can be downregulated by minocycline: possible implications for long-term treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis . VIROLOGY JOURNAL14 ( 1 ) 234 2017.12Reviewed International journal

Language：English Publisher：BIOMED CENTRAL LTD

Background: Chemokine (C-C motif) ligand 1 (CCL1) is produced by activated monocytes/macrophages and T-lymphocytes, and acts as a potent attractant for Th2 cells and a subset of T-regulatory (Treg) cells. Previous reports have indicated that CCL1 is overexpressed in adult T-cell leukemia cells, mediating an autocrine anti-apoptotic loop. Because CCL1 is also known as a potent chemoattractant that plays a major role in inflammatory processes, we investigated the role of CCL1 in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
Results: The results showed that: (1) CCL1 was preferentially expressed in HAM/TSP-derived HTLV-1-infected T-cell lines, (2) CCL1 expression was induced along with Tax expression in the Tax-inducible T-cell line JPX9, (3) transient Tax expression in an HTLV-1-negative T-cell line activated the CCL1 gene promoter, (4) plasma levels of CCL1 were significantly higher in patients with HAM/TSP than in HTLV-1-seronegative patients with multiple sclerosis and HTLV-1-infected asymptomatic healthy carriers, and (5) minocycline inhibited the production of CCL1 in HTLV-1-infected T-cell lines.
Conclusions: The present results suggest that elevated CCL1 levels may be associated with the pathogenesis of HAM/TSP. Although further studies are required to determine the in vivo significance, minocycline may be considered as a potential candidate for the long-term treatment of HAM/TSP via its anti-inflammatory effects, which includes the inhibition of CCL1 expression.

DOI： 10.1186/s12985-017-0902-6

Yuko Yamagishi, Hidekazu Suzuki, Masahiro Sonoo, Satoshi Kuwabara, Takanori Yokota, Kyoichi Nomura, Atsuro Chiba, Ryuji Kaji, Takashi Kanda, Kenichi Kaida, Shu-ichi Ikeda, Tatsuro Mutoh, Ryo Yamasaki, Hiroshi Takashima, Makoto Matsui, Kazutoshi Nishiyama, Gen Sobue, Susumu Kusunoki . Markers for Guillain-Barre syndrome with poor prognosis: a multi-center study . JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM22 ( 4 ) 433 - 439 2017.12Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Guillain-Barre syndrome (GBS) is an acute monophasic neuropathy. Prognostic tools include the modified Erasmus GBS outcome score (mEGOS), Erasmus GBS respiratory insufficiency score (EGRIS), and the increase in serum IgG levels (IgG) 2 weeks after intravenous immunoglobulin (IVIg) treatment. Given that proportions of GBS subtypes differ between Western countries and Japan, the usefulness of these tools in Japan or other countries remains unknown. We enrolled 177 Japanese patients with GBS from 15 university hospitals and retrospectively obtained mEGOS and EGRIS for all and IgG status for 79 of them. High mEGOS scores on admission or on day 7 were significantly associated with poorer outcomes (unable to walk independently at 6 months). High EGRIS scores (5 points) were associated with an increased risk for mechanical ventilation. Patients with IgG <1,108 mg/dl had significantly poorer outcomes. We suggest that mEGOS, EGRIS, and IgG in GBS are clinically relevant in Japan.

DOI： 10.1111/jns.12234

Tashiro Y, Takashima H . [Motor Symptoms of Autoimmune Encephalopathies]. . Brain and nerve = Shinkei kenkyu no shinpo69 ( 12 ) 1387 - 1399 2017.12[Motor Symptoms of Autoimmune Encephalopathies].

Noriyuki Miyaue, Satoshi Tada, Rina Ando, Hirotaka Iwaki, Hayato Yabe, Noriko Nishikawa, Masahiro Nagai, Hiroshi Takashima, Masahiro Nomoto . DAT SPECT may have diagnostic value in prodromal SCA2 patients with parkinsonism . PARKINSONISM & RELATED DISORDERS44 137 - 141 2017.11

Publisher：ELSEVIER SCI LTD

Introduction: Although spinocerebellar ataxia type 2 (SCA2) is classified as hereditary spinocerebellar degeneration, some patients present with parkinsonism before developing cerebellar ataxia.
Methods: I-123-metaiodobenzyl guanidine (I-123-MIBG) myocardial scintigraphy and/or dopamine transporter single photon emission computed tomography (DAT SPECT) using I-123-iofiupane (I-123-FP-CIT) were performed for the six patients from three SCA2 families.
Results: I-123-MIBG myocardial scintigraphy showed reduced cardiac uptake in four of five patients and an association with Lewy body disease was suggested. DAT SPECT showed decreased uptake in the striatum in all four patients who were scanned, including one patient without parkinsonism. When patterns of uptake were compared to those with Parkinson's disease, most of the patients had minimal reduction uptake in the putamen.
Conclusion: DAT SPECT is expected to be useful in differentiating SCA2 from Parkinson's disease, making an early diagnosis, and allowing early therapeutic intervention. (C) 2017 Published by Elsevier Ltd.

DOI： 10.1016/j.parkreldis.2017.08.012

Yasuo Shiohama, Tadasuke Naito, Toshio Matsuzaki, Reiko Tanaka, Takeaki Tomoyose, Hiroshi Takashima, Takuya Fukushima, Yuetsu Tanaka, Mineki Saito . Prevalence of plasma autoantibody against cancer testis antigen NY-ESO-1 in HTLV-1 infected individuals with different clinical status . VIROLOGY JOURNAL14 ( 1 ) 130 - 130 2017.7Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Detection of specific immune responses against cancer/testis antigen NY-ESO-1 was recently reported in patients with adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-infected asymptomatic carriers (ACs). However, the relationship of the responses with the HTLV-1 proviral load (PVL) and the levels of viral gene expression remain unclear.
Findings: We measured plasma levels of autoantibodies to NY-ESO-1 immunogenic tumor antigen in HTLV-1-infected individuals with different clinical status, and in healthy controls. Data were compared to tax and HBZ mRNA levels, and PVL. Plasma anti-NY-ESO-1 antibody was detectable in 13.7% (7/51) of ACs, 29.2% (38/130) of patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), and 18.9% (10/53) of patients with ATL. Anti-NY-ESO-1 plasma levels were significantly higher in patients with HAM/TSP than in patients with ATL or ACs. Anti-NY-ESO-1 levels were not associated with PVL or the expression levels of tax and HBZ mRNA among HTLV-1-infected individuals, regardless of clinical status.
Conclusions: The present results indicate the strong humoral immune response against NY-ESO-1 in natural HTLV-1 infection, irrespective of the clinical status. The higher immunoreactivity against NY-ESO-1 is not simply associated with the levels of both HTLV-1 gene expression and the number of infected cells in vivo. Rather, it might reflect chronic and generalized immune activation in infected individuals.

DOI： 10.1186/s12985-017-0802-9

Kimitoshi Hirayanagi, Yuji Okamoto, Eriko Takai, Kunihiko Ishizawa, Kouki Makioka, Yukio Fujita, Yuka Kaneko, Makoto Tanaka, Hiroshi Takashima, Yoshio Ikeda . Bilateral striatal necrosis caused by a founder mitochondrial 14459G > A mutation in two independent Japanese families . JOURNAL OF THE NEUROLOGICAL SCIENCES378 177 - 181 2017.7Reviewed International journal

Publisher：ELSEVIER SCIENCE BV

Bilateral striatal necrosis (BSN) has many causes and is characterized by unique clinical and neuroradiological features. Herein, we report a clinical and genetic analysis of three BSN cases from two independent Japanese families harboring a mitochondrial DNA (mtDNA) 14459G > A mutation located in a coding region of the NADH dehydrogenase subunit 6 gene. In the first family, two male siblings from non-consanguineous parents exhibited similar phenotypes, with infantile-onset generalized dystonia. A third sporadic case involved a male patient with a comparatively milder phenotype characterized by juvenile-onset mild truncal ataxia and parkinsonism. Cerebral magnetic resonance imaging of these cases revealed abnormal signal intensities along the bilateral putaminal area and enlarged lateral ventricle anterior horns caused by caudate nuclear atrophy, particularly in the sibling pair. The sibling-pair cases shared a homoplasmic 14459G > A mutation, and the sporadic case showed heteroplasmy of the same mutation. Additionally, all three cases harbored the 14605A > G single nucleotide polymorphism, which was previously reported as a rare synonymous variation (4.3%) in a Japanese population. Plasmid sequencing revealed a genetic linkage of these two DNA substitutions, suggesting that the three patients shared a genetic founder. Although our mtDNA analysis was only accessible using leukocytes, clinical severity might be associated with homoplasmy or heteroplasmy. In summary, it is important to evaluate potential mtDNA defects in BSN cases, regardless of familial occurrence. (C) 2017 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2017.05.015

Aya Nakamura, Ryo Tanaka, Kazushige Morishita, Hideki Yoshida, Yujiro Higuchi, Hiroshi Takashima, Masamitsu Yamaguchi . Neuron-specific knockdown of the Drosophila fat induces reduction of life span, deficient locomotive ability, shortening of motoneuron terminal branches and defects in axonal targeting . GENES TO CELLS22 ( 7 ) 662 - 669 2017.7Reviewed International journal

Language：English Publisher：WILEY

Mutations in FAT4 gene, one of the human FAT family genes, have been identified in Van Maldergem syndrome (VMS) and Hennekam lymphangiectasia-lymphedema syndrome (HS). The FAT4 gene encodes a large protein with extracellular cadherin repeats, EGF-like domains and Laminin G-like domains. FAT4 plays a role in tumor suppression and planar cell polarity. Drosophila contains a human FAT4 homologue, fat. Drosophila fat has been mainly studied with Drosophila eye and wing systems. Here, we specially knocked down Drosophila fat in nerve system. Neuron-specific knockdown of fat shortened the life span and induced the defect in locomotive abilities of adult flies. In consistent with these phenotypes, defects in synapse structure at neuromuscular junction were observed in neuron-specific fat-knockdown flies. In addition, aberrations in axonal targeting of photoreceptor neuron in third-instar larvae were also observed, suggesting that fat involves in axonal targeting. Taken together, the results indicate that Drosophila fat plays an essential role in formation and/or maintenance of neuron. Both VMS and HS show mental retardation and neuronal defects. We therefore consider that these two rare human diseases could possibly be caused by the defect in FAT4 function in neuronal cells.

DOI： 10.1111/gtc.12500

田畑健太郎, 佐野輝, 石塚貴周, 斉之平一隆, 横塚紗永子, 新井薫, 塩川奈理, 春日井基文, 中村雅之, 荒田仁, 高嶋博, 吉水宗裕 . ドパミン調節異常症候群が考えられ、修正型電気けいれん療法が著効した若年性パーキンソン病の一例 . 精神神経学雑誌 ( 2017特別号 ) S635 - S635 2017.6ドパミン調節異常症候群が考えられ、修正型電気けいれん療法が著効した若年性パーキンソン病の一例Reviewed

Satoshi Nozuma, Eiji Matsuura, Daisuke Kodama, Yuichi Tashiro, Toshio Matsuzaki, Ryuji Kubota, Shuji Izumo, Hiroshi Takashima . Effects of host restriction factors and the HTLV-1 subtype on susceptibility to HTLV-1-associated myelopathy/tropical spastic paraparesis . RETROVIROLOGY14 ( 1 ) 26 2017.4Reviewed International journal

Language：English Publisher：BIOMED CENTRAL LTD

Background: Although human T-lymphotropic virus type 1 (HTLV-1) infection is a prerequisite for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), specific provirus mutations in HAM/TSP have not yet been reported. In this study, we examined whether HAM/TSP patients had the disease-specific genomic variants of HTLV-1 by analyzing entire sequences of HTLV-1 proviruses in these patients, including familial cases. In addition, we investigated the genetic variants of host restriction factors conferring antiretroviral activity to determine which mutations may be related to resistance or susceptibility to HAM/TSP.
Results: The subjects included 30 patients with familial HAM/TSP (f-HAM/TSP), 92 patients with sporadic HAM/TSP (s-HAM/TSP), and 89 asymptomatic HTLV-1 carriers (ACs). In all 211 samples, 37 samples (18%) were classified into transcontinental subtype and 174 samples (82%) were classified as Japanese subtype. Among three groups, the percentage of transcontinental subtype in f-HAM/TSP, s-HAM/TSP and ACs was 33, 23 and 7%, respectively. The frequency of transcontinental subtype was significantly higher in both f-HAM/TSP (p < 0.001) and s-HAM/TSP (p < 0.001) than in ACs. Fifty mutations in HTLV-1 sequences were significantly more frequent in HAM/TSP patients than in ACs, however, they were common only in transcontinental subtype. Among these mutations, ten common mutations causing amino acid changes in the HTLV-1 sequences were specific to the transcontinental subtype. We examined host restriction factors, and detected a rare variant in TRIM5 alpha in HAM/TSP patients. The patients with TRIM5 alpha 136Q showed lower proviral loads (PVLs) than those with 136R (354 vs. 654 copies/10(4) PBMC, p = 0.003). The patients with the 304L variant of TRIM5 alpha had significantly higher PVLs than those with 304H (1669 vs. 595 copies/10(4) PBMC, p = 0.025). We could not find any HAM/TSP-specific mutations of host restriction factors.
Conclusions: Transcontinental subtype is susceptible to HAM/TSP, especially in familial cases. Ten common mutations causing amino acid changes in the HTLV-1 gene were specific to the transcontinental subtype. TRIM5 alpha polymorphisms were associated with PVLs, indicating that TRIM5 alpha could be implicated in HTLV-1 replication.

DOI： 10.1186/s12977-017-0350-9