Acquired Immunodeficiency Syndrome: Matsushita S

Matsushita S, Kimura T. · Division of Clinical Retrovirology and Infectious Disease, Center for AID Research, Kumamoto University. · Nippon Rinsho. · Pubmed #11808127 No free full text.

This publication has no abstract.

Kimura T, Matsushita S. · Division of Clinical Retrovirology, Center for AIDS Research, Kumamoto University. · Ryoikibetsu Shokogun Shirizu. · Pubmed #11212750 No free full text.

This publication has no abstract.

Matsushita S, Koito A. · Division of Clinical Retrovirology and Infectious Diseases, Center for AIDS Research, Kumamoto University. · Nippon Rinsho. · Pubmed #11197842 No free full text.

Abstract: Following the introduction of HAART(highly active anti-retroviral therapy) marked decreases in AIDS-related morbidity and mortality have been observed. Despite of the clinical success, recent work suggests that there are persistent viral replication in whom plasma HIV-RNA is consistently below detectable level. Furthermore, some experts even suggest that it will be difficult for many of the patients to continue the HAART because of the long-term side effects and drug resistance. Recent studies that supported the correlation of HIV-specific CD4-T cell(helper) response with the control of viral replication in vivo have promoted the development gene-based immunotherapy. However, further elucidation of viral pathogenesis in the patient under HAART will be required to develop the immunotherapeutic interventions.

Murakami T, Nakajima M, Nakamura T, Hara A, Uyama E, Mita S, Matsushita S, Uchino M. · Department of Neurology, Kumamoto University School of Medicine. · Intern Med. · Pubmed #11197803 links to  free full text

Abstract: We studied a Japanese patient who developed parkinsonian symptoms over 3 months before the diagnosis of acquired immunodeficiency syndrome. Brain MRI showed multiple lesions with mass effect and ring enhancement in the basal ganglia and subcortical white matter suggesting Toxoplasma infection. Anti-Toxoplasma therapy and highly active antiretroviral therapy for 6 months allowed improvement of parkinsonism, brain MRI findings, and immune system.

Matsushita S. · Division of Clinical Retrovirology and Infectious Diseases, Center for AIDS Research, Kumamoto University, Japan. · Gan To Kagaku Ryoho. · Pubmed #10431574 No free full text.

Abstract: Following the introduction of highly active anti-retroviral therapy (HAART), which uses a combination of chemotherapeutic agents including protease inhibitors a striking reduction in overall HIV mortality and morbidity has been observed. In Japan ten anti-retroviral agents (five nucleoside reverse-transcriptase inhibitors, one non-nucleoside reverse-transcriptase inhibitor and four protease inhibitors) have been approved and tentative guidelines for the use of these agents were proposed by some groups of investigators. After the introduction of HAART, however, new problems such as the emergence of mutants that are resistant to any available drugs and the long-term adverse effects of some antivirals have appeared. Further investigation into the new therapeutic strategies including immunotherapy, as well as the efforts to develop antiretroviral agents that overcome resistance, are urgently needed.

Ryo A, Tsurutani N, Ohba K, Kimura R, Komano J, Nishi M, Soeda H, Hattori S, Perrem K, Yamamoto M, Chiba J, Mimaya J, Yoshimura K, Matsushita S, Honda M, Yoshimura A, Sawasaki T, Aoki I, Morikawa Y, Yamamoto N. · Department of Pathology, Yokohama City University School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan. · Proc Natl Acad Sci U S A. · Pubmed #18172216 links to  free full text

Abstract: Human immunodeficiency virus type 1 (HIV-1) utilizes the macromolecular machinery of the infected host cell to produce progeny virus. The discovery of cellular factors that participate in HIV-1 replication pathways has provided further insight into the molecular basis of virus-host cell interactions. Here, we report that the suppressor of cytokine signaling 1 (SOCS1) is an inducible host factor during HIV-1 infection and regulates the late stages of the HIV-1 replication pathway. SOCS1 can directly bind to the matrix and nucleocapsid regions of the HIV-1 p55 Gag polyprotein and enhance its stability and trafficking, resulting in the efficient production of HIV-1 particles via an IFN signaling-independent mechanism. The depletion of SOCS1 by siRNA reduces both the targeted trafficking and assembly of HIV-1 Gag, resulting in its accumulation as perinuclear solid aggregates that are eventually subjected to lysosomal degradation. These results together indicate that SOCS1 is a crucial host factor that regulates the intracellular dynamism of HIV-1 Gag and could therefore be a potential new therapeutic target for AIDS and its related disorders.

Nakayama EE, Carpentier W, Costagliola D, Shioda T, Iwamoto A, Debre P, Yoshimura K, Autran B, Matsushita S, Theodorou I. · Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka, Japan. · Immunogenetics. · Pubmed #17406861 No free full text.

Abstract: Polymorphisms in human genes have been shown to affect the rate of disease progression to acquired immune deficiency syndrome in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Recently, tripartite motif 5alpha (TRIM5alpha) was identified as a factor that confers resistance to HIV-1 infection in Old World monkey cells. Subsequently, Sawyer et al. (Curr Biol 16:95-100, 2006) reported a single nucleotide polymorphism (H43Y) in the human TRIM5alpha gene and TRIM5alpha protein with 43Y was found to lose its ability to restrict HIV-1. In the present study, we reevaluated effects of this allele on in vitro anti-HIV-1 activity as well as on HIV-1 disease progression in European and Asian cohorts of HIV-1-infected individuals. Our epidemiological and molecular biological findings clearly indicate H43Y has a very minor effect on anti-HIV-1 activity of TRIM5alpha, suggesting that this allele is immaterial, at least in HIV-1-infected Europeans and Asians.

Eda Y, Murakami T, Ami Y, Nakasone T, Takizawa M, Someya K, Kaizu M, Izumi Y, Yoshino N, Matsushita S, Higuchi H, Matsui H, Shinohara K, Takeuchi H, Koyanagi Y, Yamamoto N, Honda M. · AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan. · J Virol. · Pubmed #16699037 links to  free full text

Abstract: In an accompanying report (Y. Eda, M. Takizawa, T. Murakami, H. Maeda, K. Kimachi, H. Yonemura, S. Koyanagi, K. Shiosaki, H. Higuchi, K. Makizumi, T. Nakashima, K. Osatomi, S. Tokiyoshi, S. Matsushita, N. Yamamoto, and M. Honda, J. Virol. 80:5552-5562, 2006), we discuss our production of a high-affinity humanized monoclonal antibody, KD-247, by sequential immunization with V3 peptides derived from human immunodeficiency virus type 1 (HIV-1) clade B primary isolates. Epitope mapping revealed that KD-247 recognized the Pro-Gly-Arg V3 tip sequence conserved in HIV-1 clade B isolates. In this study, we further demonstrate that in vitro, KD-247 efficiently neutralizes CXCR4- and CCR5-tropic primary HIV-1 clade B and clade B' with matching neutralization sequence motifs but does not neutralize sequence-mismatched clade B and clade E isolates. Monkeys were provided sterile protection against heterologous simian/human immunodeficiency virus challenge by the passive transfer of a single high dose (45 mg per kg of body weight) of KD-247 and afforded partial protection by lower antibody doses (30 and 15 mg per kg). Protective neutralization endpoint titers in plasma at the time of virus challenge were 1:160 in animals passively transferred with a high dose of the antibody. The antiviral efficacy of the antibody was further confirmed by its suppression of the ex vivo generation of primary HIV-1 quasispecies in peripheral blood mononuclear cell cultures from HIV-infected individuals. Therefore, KD-247 promises to be a valuable tool not only as a passive immunization antibody for the prevention of HIV infection but also as an immunotherapy for the suppression of HIV in phenotype-matched HIV-infected individuals.

Yoshimura K, Ido E, Akiyama H, Kimura T, Aoki M, Suzuki H, Mitsuya H, Hayami M, Matsushita S. · Division of Clinical Retrovirology and Infectious Diseases, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto, 860-0811, Japan. · J Virol Methods. · Pubmed #12951220 No free full text.

Abstract: The objective of this study was to assess the impact of highly active antiretroviral therapy (HAART) by an oral route on the peripheral blood CD8 subset in the monkeys infected persistently with a pathogenic strain, SHIV(89.6P). Two rhesus macaques were inoculated intravenously with SHIV(89.6P), then treated with the combination of AZT, 3TC and Lopinavir/Ritonavir (LPV/RTV) as recommended in humans by the oral route with confectionery continued for 28 days. In one of two chronically infected macaques, MM260, the viral load was maintained in the range of 10(4)-10(5) copies/ml before HAART. The plasma viral load and proviral DNA decreased dramatically during the treatment, and cessation of this therapy the viral load rebounded to the pre-treatment level but the proviral DNA rebound was delayed. The other monkey, MM242, had low viral loads (1.2x10(3)-<5x10(2) copies/ml) both before and after HAART. CD4(+) and CD8(+) T cell counts and proviral DNA level were not significantly changed after the treatment. The percentages of CD8(+)CD45RA(-)Ki67(+)cells increased during (MM260) or after (MM242) HAART and the subset was maintained at a high percentage until 18 weeks post HAART in MM242. These findings suggest that this primate model might serve an important role in testing the virological and immunological efficacy of novel therapeutic strategies combined with HAART.