Human T-cell Leukemia Virus Type I Infection Research Articles

Mediators of central nervous system damage during the progression of human T-cell leukemia type I-associated myelopathy/tropical spastic paraparesis.

Human T-cell leukemia virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) represents one of the most devastating diseases associated with HTLV-I infection. Despite the delineation of clinical features associated with this neurologic disease, more progress needs to be made with respect to understanding the molecular mechanisms relating to the genesis of HAM/TSP. Several factors have been hypothesized to contribute to whether an HTLV-I-infected individual remains asymptomatic, develops adult T-cell leukemia (ATL), or progresses to HAM/TSP. Among the most intriguing of these factors is the immune response mounted by the host against HTLV-I. Several cell populations are crucial with respect to generating an efficient immune response against the virus. This includes CD4(+) T cells, CD8(+) T cells, dendritic cells (DCs), monocytes/macrophages, and HTLV-I-infected cells that interact with immune cells to stimulate their effector functions. Although all of these cell types likely play important roles in the etiology of HAM/TSP, this review focuses specifically on the potential function of the CD8(+) T-cell population during the progression of HTLV-I-induced neurologic disease. The immune response in HAM/TSP patients may transition from a beneficial response aimed at controlling the viral infection, to a detrimental response that ultimately participates in mediating the pathology observed in HAM/TSP. In this respect, the generation of a hyperactive CD8(+) cytotoxic T lymphocyte (CTL) response primarily targeting the HTLV-I Tax protein likely plays a key role in the genesis of pathologic abnormalities associated with HAM/TSP. The efficiency and activity of Tax-specific CD8(+) CTLs may be regulated at a number of levels, and deregulation of Tax-specific CTL activation may contribute to HAM/TSP. This review focuses on potential mechanisms of central nervous system (CNS) damage associated with the genesis of HAM/TSP following HTLV-I infection, focusing on the role of the Tax-specific CTL compartment.

Regulation of IFN regulatory factor 4 expression in human T cell leukemia virus-I-transformed T cells.

IFN regulatory factor (IRF)-4 is a lymphoid/myeloid-restricted member of the IRF transcription factor family that plays an essential role in the homeostasis and function of mature lymphocytes. IRF-4 expression is tightly regulated in resting primary T cells and is transiently induced at the mRNA and protein levels after activation by Ag-mimetic stimuli such as TCR cross-linking or treatment with phorbol ester and calcium ionophore (PMA/ionomycin). However, IRF-4 is constitutively upregulated in human T cell leukemia virus type I (HTLV-I) infected T cells as a direct gene target for the HTLV-I Tax oncoprotein. In this study we demonstrate that chronic IRF-4 expression in HTLV-I-infected T lymphocytes is associated with a leukemic phenotype, and we examine the mechanisms by which continuous production of IRF-4 is achieved in HTLV-I-transformed T cells. IRF-4 expression in HTLV-1-infected cells is driven through activation of the NF-kappaB and NF-AT pathways, resulting in the binding of p50, p65, and c-Rel to the kappaB1 element and p50, c-Rel, and NF-ATp to the CD28RE element within the -617 to -209 region of the IRF-4 promoter. Furthermore, mutation of either the kappaB1 or CD28RE sites blocks Tax-mediated transactivation of the human IRF-4 promoter in T cells. These experiments constitute the first detailed analysis of human IRF-4 transcriptional regulation within the context of HTLV-I infection and transformation of CD4(+) T lymphocytes.

HTLV-I Protease Cleavage of P19/24 Substrates Is Not Dependent on NaCl Concentration

Understanding the factors that affect the activity of Human T-cell Leukemia Virus type I (HTLV-I) protease is essential for the discovery of inhibitors to be used for the treatment of HTLV-I infection, but little has been reported on the protease to date. Here we report the production of HTLV-I protease in purified yields greater than 150 mg/L, determination of its extinction coefficient, and determination of the optimum conditions for cleavage of the p19/24 substrates (DABCYL)-(GABA)-PQVL-Nph-VMH-(EDANS), (DABSYL)-(GABA)-PQVL-Nph-VMH-(EDANS), and (DABSYL)-(GABA)-PQVLPVMH-(EDANS). The highest activity was found at pH 5.2-5.3 and 37°C. There was no effect on activity upon change in sodium chloride concentration from 0 to 1500 mM. The values of Km and kcat for cleavage of these substrates by the protease with and without the histidine tag were determined.

Human T-cell leukemia virus type I Tax transactivates the matrix metalloproteinase-9 gene: potential role in mediating adult T-cell leukemia invasiveness

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL) and of tropical spastic paraparesis/HTLV-I-associated myelopathy. Infiltration of various tissues by circulating leukemic cells is a characteristic of ATL. Matrix metalloproteinases (MMPs), which mediate the degradation of the basement membrane and extracellular matrix, play an important role in metastasis and tumor cell dissemination. The aim of this study was to explore whether expression of MMP-2 and MMP-9 was deregulated by HTLV-I infection. The data showed that HTLV-I-infected T-cell lines expressed high levels of MMP-9 compared with uninfected T-cell lines. In contrast, the levels of the related MMP-2 were not significantly altered by HTLV-I infection. In addition, the elevated expression of MMP-9 in HTLV-I-infected cells was attributable to the action of the viral transactivator protein Tax. The results show that Tax can activate the MMP-9 promoter and induce MMP-9 expression in T cells, indicating that the constitutive expression of MMP-9 in virus-infected cell lines is at least in part mediated by Tax. Activation of the MMP-9 promoter by Tax occurs mainly through the action of NF-kappaB and SP-1. The biologic significance of these observations was validated by the following 2 findings: MMP-9 expression was increased in primary ATL cells, and plasma MMP-9 levels were elevated in ATL patients. In addition, plasma levels of MMP-9 correlated with organ involvement in ATL patients. Together these data suggest that overexpression of MMP-9 in HTLV-I- infected cells may be in part responsible for the invasiveness of ATL cells.

Analysis of the infection system of human T-cell leukaemia virus type I based on a mathematical epidemic model.

Human T-cell leukaemia virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukaemia (ATL). HTLV-I has existed in Japanese people for thousands of years. In order to prevent an epidemic of HTLV-I, it is important to explain the infection system by a mathematical approach. By considering the main infection routes in Japan, that is: (i) mother-to-child transmission; (ii) male (husband)-to-female (wife) transmission; and (iii) female (wife)-to-male (husband) transmission, a mathematical model for describing the time-dependent change of the infection proportion can be constructed. An upper bound of the present infection rate per year in male-to-female transmission and that in female-to-male transmission is given by the model, and theoretical results related to HTLV-I infection are also deduced from the mathematical model. A simulation study based on the present model demonstrates the theoretical results relating to the HTLV-I infection.

Direct vs. indirect modulation of complex in vitro human retroviral infections by morphine.

BACKGROUND The human T-cell leukemia virus type I (HTLV-I) was first characterized by Gallo in 1981 1. This type C oncoretrovirus was thought to be confined to well-delineated regions, passed primarily by long-term exposure (i.e., mother to infant, long-term marital relationships) or by frequent exposure to large numbers of infected cells. No recent largescale epidemiological studies showing the incidence of HTLV-I infection in the United States are available, however, it is estimated that current infection rates are somewhat higher than previously believed. A significant contribution to the estimated increase in HTLV-I infection in the U.S., as well as to the confirmed increases worldwide, is associated with injecting drug users (IDU) 1,2 . This route of infection is more efficiently exploited by human immunodeficiency virus type 1 (HIV-1). Both retroviruses target the same CD4+ lymphocytes, however an opposite set of outcomes is observed with HTLV-I versus HIV-1 infection. The decimating influence of HIV-1 on CD4+ T cell populations has been well documented and is thought to be responsible for the onset of AIDS. In contrast, a hallmark of active HTLV-I infection is the inappropriate proliferation of CD4+ T cells, expressed as HLTV-I associated myelopathy (TSP/HAM) or as adult T cell lymphoma (ATL). Additional disorders related to HTLV-I infection are also dependent upon uncontrolled T cell proliferation. Although the characteristics of infection are different, the lentivirus (HIV-1) and the oncoretrovirus (HTLV-I) produce somewhat analogous proteins that have been reported to act in a complementary fashion in vitro. Thus, the possibility that superinfection with HIV1 and HTLV-I in an individual might enhance the progression of HIV-1 infection was investigated during several large-scale epidemiological studies. Earlier case studies using small numbers of coinfected patients suggested that symptoms of complex retroviral infections (dual infection with HIV-1 and HTLV-I) were different from simple HIV-1 infection. However, the larger studies failed to demonstrate a consistent reduction in the

Evidence for Humoral and Cellular Reactivity Against Keratin and Thyroglobulin in HTLV-I Infected Rabbits

Human T cell leukemia virus type I (HTLV-I) infection was initially associated with T cell leukemia and a progressive neurologic disease but has since been linked to an increasing number of autoimmune disorders, including Sjogren's syndrome, uveitis, and polyarthritis. A survey of serum samples from a rabbit model of HTLV-I infection revealed that all had antibodies against keratin and thyroglobulin. Sera from several infected rabbits also reacted with collagen, while antibody reactions with other autoantigens tested, including DNA, were rare and sporadic. In addition to antibodies, cellular reactivity to keratin, but not thyroglobulin, was demonstrated by cellular proliferation in presence of 11.-2 and keratin. Expanded cell cultures were positive for T cell activation markers and CD8. Association of the auto-reactivity with HTLV-I infection rather than random anti-cellular responses was supported by the fact that no antikeratin or antithyroglobulin was seen in uninfected controls, including that inoculated with uninfected lymphocytes. Finding autoantibodies in rabbits infected using naked HTLV-I DNA clones provided further assurance that infection induced the autoimmune reactions detected.

特発性血小板減少性紫斑病の診断より９年４カ月後にサルコイドーシスを発症したＨＴＬＶ‐Ｉキャリア

A 48-year-old female presented a bleeding tendency due to thrombocytopenia (7000/μ1) in August 1990. She was diagnosed as having idiopathic thrombocytopenic purpura (ITP), and splenectomy was carried out in May, 1991. Her peripheral platelet count increased to the normal level after that, and she was followed up at our hospital regularly in healthy condition.But, skin eruptions appeared transciently in August 1995, and a recurrent, persistent cough like chronic bronchitis bothered her from June 1996. She suffered from herpes zoster of the right trigeminal nerve in sudden, and had hospitalization in December 1998.Her chest X-ray film presented the bilateral hilar lymphadenopathy on admission, so several further examinations were done. As results, she was proved to be a human T-cell leukemia virus-type I (HTLV-I) carrier, and biopsy spacimens of her left upper-lung established the diagnosis of sarcoidosis.The clinical process of HTLV-I infection, ITP, and sarcoidosis in this case makes us take it into consideration that the pathophysiological mechanism of ITP might have a possible etiological relationship with HTLV-I infection, which can be responsible for the increased antiplatelet T helper lymphocyte reactivity in patients with ITP.

Low prevalence of Helicobacter pylori in individuals with HTLV-I infection

The prevalence of Helicobacter pylori in HIV-positive individuals is significantly lower than in HIV-negative controls. However, its prevalence in individuals infected with human T-cell leukaemia virus type I (HTLV-I), another important member of the human retrovirus family, has not been previously investigated. To establish the prevalence of H. pylori in HTLV-I-positive individuals in the Nagasaki Prefecture, which is an area endemic for HTLV-I. We examined sera from 146 HTLV-I-positive individuals with a mean age of 56.7 years, consisting of 45 adult T-cell leukaemia (ATL) patients, 13 HTLV-I-associated myelopathy (HAM) patients and 88 healthy carriers. Serum samples of 292 age- and sex-matched HTLV-I-negative controls were also examined. Serum anti-H. pylori immunoglobulin (Ig) G antibody was examined using an enzyme-linked immunosorbent assay kit. Twenty-eight HTLV-I-positive patients were examined endoscopically, assessed for H. pylori by culture, histology and CLO test using gastric biopsy specimens, and gastritis in these patients was also graded histologically. The seroprevalence of H. pylori was 48% in HTLV-I-positive individuals versus 64% in HTLV-I-negative controls (P < 0.01). In the three HTLV-I-positive groups, ATL patients and carriers had significantly lower seroprevalence of H. pylori than the HTLV-I-negative controls (P < 0.05). Assessment of H. pylori using gastric biopsy specimens also showed a significantly lower prevalence of H. pylori infection in HTLV-I-positive patients than controls (46% versus 70%, P < 0.05). Histological examination showed a significantly higher degree of activity, inflammation and glandular atrophy in the antrum and corpus in H. pylori-positive patients compared to H. pylori-negative patients. H. pylori-positive patients with HTLV-I infection had a more severe degree of glandular atrophy in the corpus than H. pylori-positive controls without HTLV-I infection. We have found a reduced prevalence of H. pylori in HTLV-I-positive individuals. Whatever the explanation, infection with HTLV-I does not predispose to the risk of H. pylori infection.

Morphine effects on HTLV-I infection in the presence or absence of concurrent HIV-1 infection.

Human T-cell leukemia virus type I (HTLV-I) infection is emerging as an important complication in HIV infection and AIDS in injecting drug users. HIV-1 and HTLV-I share a common host in CD4+ T lymphocytes. However, the result of HIV-1 infection is the decimation of this cell population, whereas a hallmark of HTLV-I infection is the inappropriate proliferation of infected cells. Combined epidemiologic data suggest that HTLV-I infection is enhanced during concurrent HIV-1/HTLV-I infection; however, there are currently no in vitro studies focusing on the effects of drugs of abuse on retrovirus coinfection. We have found that in an in vitro coinfection system (HIV-1 + HTLV-I), morphine treatment further enhanced the levels of HTLV-I p19. In addition, indicators of in vitro infection by cell-free HIV-1 were reduced by morphine treatment in both single and dual in vitro infection experiments. Interleukin 2 levels in the affected cultures were found to increase with combined HTLV-I infection and morphine treatment. These in vitro results indicate the need to further explore the activity of HTLV-I within opiate-treated cells, as this oncoretrovirus appears to be especially sensitive to morphine-induced alterations to its host cell environment.

LEUKEMOGENESIS AND PROGRESSION OF ADULT T-CELL LEUKEMIA

O-15 Following infection with human T-cell leukemia virus type I (HTLV-I), a long latent period is required for the development of frank adult T-cell leukemia (ATL), suggesting that accumulated genetic or epigenetic changes of the host genes are involved in leukemogenesis. In HTLV-I+ carriers, CD4+ memory T-cells increase in accordance with HTLV-I provirus load. In contrast, both CD4+ and CD8+ naive T-cells decrease, which might account for the immunodeficiency associated with HTLV-I infection. Phenotypes of increased CD4 memory T-cells are similar to those of ATL cells, suggesting that HTLV-I viral protein(s), especially Tax, promotes the proliferation of infected cells, leading to the onset of ATL. Cyclin-dependent kinase inhibitor, p16 gene, is one of tumor suppressor genes, whose deletions have been shown to be associated with high-grade malignant ATL. We examined the methylation profile of p16 in various HTLV-I-infected cell populations using methylation-specific PCR (MSPCR) following sodium bisulfite treatment. A high frequency of methylation of p16 gene was identified in ATL samples and HTLV-I-transformed cell lines. Sequencing of p16 revealed that the CpG sites of p16 were more frequently methylated in fresh leukemic cells than detected with MSPCR. Fresh leukemic cells isolated from acute and lymphoma-type ATL cases had more methylated sites than those from chronic or smoldering ATL cases. These data suggest that the CpG sites of p16 are methylated at greater levels as the disease progresses, resulting in the suppression of p16 expression. Although Tax has been shown to functionally inactivate p16, the methylation of p16 also appears to play a critical role in regulating p16 in HTLV-I-associated leukemogenesis.

INDUCTION OF ATL-LIKE LYMPHOPROLIFERATIVE DISEASE AND ITS PREVENTION BY ADOPTIVE IMMUNOTHERAPY IN T-CELL DEFICIENT NUDE RATS INOCULATED WITH SYNGENIC HTLV-I-IMMORTALIZED CELLS

SP-09 Human T-cell leukemia virus type I (HTLV-I) has been shown to be the oncogenic agent of adult T cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In this study, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation of various rat HTLV-I immortalized cell lines. When we inoculated previously established cell lines, some of them developed systemic multiple tumors in adult nude (nu/nu) rats. FPM1 cells, newly established from a hetero (nu/+) rat syngenic to nude rats, caused transient tumors only at the injection site in adult nu/nu rats, but could progressively grow in new born nu/nu rats and metastasize in lymph nodes. The derivative cell line (FPM1-V1AX) serially passed through newborn nu/nu rats acquired the potency to grow in adult nu/nu rats. These results indicated that only some with additional changes but not all the in vitro HTLV-I immortalized cell lines possessed in vivo tumorigenicity. Using the syngenic system, we further showed the inhibition of tumor development by transferring splenic T cells from immunized rats, suggesting the involvement of T cells in the regression of tumor. This nude rat model of human ATL will be useful for further investigation of both leukemogenesis and anti-tumor immune responses in HTLV-I infection.

Quantification of proviral DNA load in human T-cell leukaemia virus type I infections

A nested PCR was designed using primers from the pol and tax genes of human T-cell leukaemia virus type I (HTLV-I). The assay reliably detected a single copy of HTLV-I proviral genome in DNA from 1×10 5 Peripheral blood mononuclear cells (PBMCs). Using serial dilutions of sample DNA, the assay was applied prospectively to study proviral load in patients with HTLV-associated disease and carriers. The median proviral load expressed as number of copies/100 PBMCs was found to be 14.0 copies in patients with HAM and 1.55 copies in initially asymptomatic carriers. The assay was used to test for low proviral load in subjects who may have HTLV-I infection, and to monitor response to therapy.

Identification of membrane antigens important for adsorption of human T-cell leukaemia virus type I

We isolated three monoclonal antibodies (mAbs), H3e, H11b and H16h, which were capable of inhibiting syncytium formation induced in a human T-cell line MOLT-4 or a human glioma line U251 MG by coculture with human T-cell leukaemia virus type I (HTLV-I)-positive human T-cell lines. The mAbs partially inhibited the plating of pseudotypes of vesicular stomatitis virus (VSV) bearing envelope antigens of HTLV-I. Formation of proviral DNA was also inhibited when indicator cells were treated with the mAbs before adsorption of HTLV-I, but not after its adsorption. They did not inhibit syncytium formation induced by human immunodeficiency virus type 1. Flow cytometry revealed that H16h hardly reacted with various HTLV-I-positive T cells, while H3e and H11b reacted with HTLV-I-positive human cells as well as HTLV-I-negative human cells. H11b and H16h immunoprecipitated the membrane antigen with a molecular weight of 20 and 110-130 kDa, respectively. Western blot analysis showed that H3e, H11b and H16h bound to the protein of 20, 20 and 110-130 kDa, respectively. Thus, these findings suggest that the 20- and 110-130-kDa cell surface proteins may play a role at the early stage of HTLV-I infection.

Relationship between Anti-Tax Antibody Responses and Cocultivatable Virus in HTLV-I-Infected Rabbits

The presence of anti-Tax antibody responses in human T cell leukemia virus type I (HTLV-I)-infected individuals has been correlated with increased proviral load, increased risk of transmitting infection, and increased risk of developing tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). In this study, a rabbit model of HTLV-I infection was used to determine whether anti-Tax antibody responses could predict the presence of virus with the potential to replicate. Seven of 14 HTLV-I-infected rabbits developed anti-Tax antibody responses. The onset of Tax reactivity was variable, but once detected remained constant throughout the remainder of the 60-week course of the study. All anti-Tax antibody positive rabbits produced virus as measured by p19 expression upon coculture, while p19 was detected in only one of the Tax antibody negative animals. Thus the presence of an anti-Tax antibody response correlates with p19 expression following cocultivation, and may be a useful predictor of virus replication in HTLV-I infected individuals.

Source and route of exposure influence infectivity of a molecular clone of human T cell leukemia virus type I.

Infection with human T cell leukemia virus type I (HTLV-I) is typically asymptomatic, but does result in diverse diseases ranging from adult T cell leukemia to spastic neuromyelopathy. To date, differences in HTLV-I provirus structure have not been correlated with pathogenic or asymptomatic outcome of infection. Molecular clones of HTLV-I are now available and represent a powerful tool to link virus structure to pathogenesis. Present studies to explore in vivo infectivity and pathogenicity of an HTLV-I molecular clone, K30p, have utilized the rabbit as a model system. This clone was administered to neonatal or adult rabbits by several different routes and infectivity and pathogenicity were examined. Detection of antiviral humoral immune responses, presence of provirus in tissue samples, and isolation of virus in cultures of blood lymphocytes were used to establish systemic HTLV-I infection. Intramuscular, but not nervous system, exposure to K30p HTLV-I naked DNA resulted in infection. Conversely, neural exposure to T cells that had been transfected with the K30p HTLV-I DNA consistently resulted in systemic infection. Despite detection of HTLV-I provirus in brain and spinal cord of some infected rabbits, no clinical or neuropathological changes occurred. Source and route of virus exposure played a role in infectivity, but did not influence the pathogenic outcome of HTLV-I infection.

Interleukin-10 Gene Expression and Adult T-Cell Leukemia

Numerous studies have shown spontaneous IL-10 gene expression and synthesis in a variety of peripheral blood or bone marrow-derived leukemic cells. These include B-cells derived from various lymphoproliferative disorders. Since little is known regarding IL-10 expression in leukemic T-cells, we examined clinical specimens of patients with adult T-cell leukemia (ATL) for IL-10 expression. Sera from ATL patients show increased levels of IL-10 when compared with sera from healthy donors. IL-10 is constitutively produced by ATL cells and also by human T-cell leukemia virus type I (HTLV-I)-infected cell lines. It is thought that HTLV-I infection induces gene expression for IL-10. In this review, a transcriptional regulation of IL-10 gene expression by HTLV-I Tax and the possible role of the NF-KB pathway are described.

Immunoreactivity and conformation of the immunodominant domain of HTLV-I envelope surface glycoprotein

The envelope of the human retrovirus HTLV-I (human T-cell leukemia virus type I), like those of other retroviruses, plays an important role in viral infection. One of the major immunodominant domains of HTLV-I surface glycoprotein (gp46), inducing antibody reactions in over 90% of infected individuals, is bounded by amino acids 175 and 199. As compared to HTLV-I prototype strain MT-2, few amino acid substitutions have been described in this region; the most frequently observed is the replacement of a proline by a serine at position 192. In order to investigate the antigenic impact of this variation, we analysed the reactivity of synthetic peptides, harbouring either a proline or a serine residue, towards antibody containing HTLV-I positive sera in enzyme linked immunosorbent assays. The possible influence of this amino acid substitution on the conformational behaviour has been examined by studying the solution structure of two model peptides (corresponding to the 175–199 region) using two-dimensional1H NMR spectroscopy. The results of this work should allow us to find out whether this amino acid substitution has to be taken into account for the design of a future peptide-based vaccine against HTLV-I infection.

Effect of phospholipids on adsorption and penetration of human T-cell leukemia virus type I

We have studied the ability of some phospholipids (PLs) and phospholipases (PLases) to interfere with infection of human T-cell leukemia virus type I (HTLV-I). Plating of pseudotype of vesicular stomatitis virus (VSV) bearing envelope antigens of HTLV-I, VSV(HTLV-I), was markedly inhibited by treatment of the cells with cardiolipin (CL) after, but not before, infection. Treatment of the cells with CL after infection also inhibited the plating of VSV pseudotype of bovine leukemia virus (BLV), but scarcely affected VSV infection. Furthermore, the plating of VSV(HTLV-I) was markedly enhanced by treatment with PLCase after infection. Treatment with PLCase, however, did not affect the plating of VSV. These results were also confirmed by polymerase chain reaction (PCR): Formation of proviral DNA was inhibited when indicator cells were treated with CL after cell-free infection of HTLV-I, but not before, and enhanced when indicator cells were treated with PLCase after HTLV-I infection. These findings suggested that PLs might play a role at the early stage of HTLV-I infection.

Prophylaxis of experimental HTLV-I infection in cynomolgus monkeys by passive immunization

The protective effect of purified human immunoglobulin against human T-cell leukaemia virus type I (HTLV-I), designated ATLIG on HTLV-I infection was examined in cynomolgus monkeys ( Macaca fascicularis) as a preclinical study. Passive immunization of ATLIG 24 h before challenging HTLV-I protected the monkeys from HTLV-I infection. The result suggests that passive immunization of ATLIG could provide safe and sufficient protection against HTLV-I infection in humans.