Introduction

This laboratory joined in the cooperative graduate school system, as an "affiliated laboratory" of the Nagoya University Graduate School of Medicine in 2009. Our laboratory is located at Clinical Research Center, National Hospital Organization Nagoya Medical Center. The research center was inaugurated on May 1st. 1976 in the National Hospital Organization, Nagoya Medical Center at Naka-ku, Nagoya city near Nagoya Castle, and consists of 5 departments (Advanced Diagnosis, Regenerative Medicine, Clinical Research Promotion, Hematology and Oncology Research, and Infectious Diseases and Immunology). Our research group, department of "Infectious Diseases and Immunology", investigates on basic and clinical sciences for human immunodeficiency viruses (HIV) and the related pathogen-infectious diseases "from bench top through bed side.
In Japan, more than 1,000 people per year are newly diagnosed with HIV at present, and unfortunately, the incidence is still increasing, particularly around Nagoya area. Recent therapies using combinations of anti-HIV drugs have improved the disease progression of the HIV-infected people. However, since the drug therapies must be under the long-term control, we must consider the presumable problem facing the appearance and development of resistance in the virus. To avoid such problem, it is quite requisite to understand how the virus develops resistance to anti-HIV drugs, to survey how such drug-resistant viruses spread in Japan epidemiologically, and to develop more effective strategies for treating HIV infection. Therefore, our research team devotes all the efforts to investigate the fundamental studies by setting up the following five specific projects; 1) Epidemiological survey of drug-resistant HIV in Japan, collaborating with prefectural and municipal public health institutes, National Institutes of Infectious Diseases, and universities. 2) Analysis of molecular/structure-biological mechanism for drug-resistant viruses, 3) Development of anti-HIV compounds having novel targets, 4) Epidemiological and genetical investigations of infectious pathogens related to HIV infection, such as Hepatitis B, C viruses. 5) Analysis of molecular mechanism on anti-HIV factors derived from the host, such as APOBEC3 family, and the application/development for new anti-HIV therapies.

Research Projects

1. Epidemiological Investigation of Drug-resistant HIV in Japan

The emergence and transmission of drug-resistant HIV-1 compromise anti-retroviral treatment for HIV-1. Thus, testing for drug resistance is recommended at diagnosis and before initiating combination Antiretroviral therapy (cART). Our group has been conducting an epidemiological survey enrolling newly diagnosed patients since 2003 in collaboration with our nationwide surveillance network. Since 2012, we have also introduced genotypic tests for HIV-1 integrase inhibitor resistance. Recent prevalence of drug-resistant HIV-1 among 7,506 patients, consisting mainly of Japanese men in their late-30s and infected through male-to-male sexual contacts, has been in a constant level, around 8% in 2015 (Figure 1). The predictive factor for drug-resistant HIV-1 transmission was subtype B and those for recent HIV-1 infection were male gender, MSM behavior, Japanese nationality, and subtype B. Our surveillance studies will help raising awareness of the risks of HIV-1 infection as well as understanding trends of the HIV-1 epidemic in Japan.

2. Analysis of Molecular Mechanism for Anti-HIV and Retroviral Host Factors

Human APOBEC3 proteins are cellular cytidine deaminases that potently restrict the replication of retroviruses by hypermutating viral cDNA and/or inhibiting reverse transcription. There are seven members of this family including APOBEC3A, B, C, D, F, G, and H, all encoded in a tandem array on human chromosome 22. APOBEC3F, G, and H are the most potent inhibitors of HIV-1, but only in the absence of the virus-encoded protein, Vif. HIV-1 utilizes Vif to abrogate APOBEC3 functions in the producer cells. More specifically, Vif, serving as a substrate receptor, facilitates ubiquitination of APOBEC3 proteins by forming a Cullin5-based E3 ubiquitin ligase complex, which targets APOBEC3 proteins for rapid proteasomal degradation. Our group investigates on the molecular mechanisms of the APOBEC3-mediated antiviral activity and of the Vif-mediated antagonism against APOBEC3. In addition, we are exploring novel strategies aiming at disrupting the APOBEC3-Vif interactions (Figure 2) to develop new antiviral inhibitors utilizing potential endogenous inhibitors against HIV-1.

Faculty Members

Faculty	Position	Department
IWATANI Yasumasa	Professor	AIDS Research

Bibliography

• 2025

  1. KA Skorupka, K Matsuoka, B Hassan, R Ghirlando, V Balachandran, T Chen, KJ Walters, CA Schiffer, M Wolf, Y Iwatani, H Matsuo. HIV-1 Vif Mediates Ubiquitination of the Proximal Protomer in the APOBEC3H Dimer to Induce Degradation. Nature Communications. 2025; 16: 5879.
  2. M Kidiga, M Murata, P Grover, H Ode, Y Iwatani, Y Seki, M Kuramitsu, M Morimoto, T Natsume, A Kaneko, S Hayashi, J Yasunaga, M Matsuoka, T Mizukami, H Akari. Identification of occult STLV-1 infection in Japanese macaques. Journal of Infectious Diseases. 2025; in press.
  3. P Grover, M Murata, M Kidiga, S Hayashi, H Ode, Y Iwatani, M Morimoto, T Natsume, A Kaneko, J Yasunaga, M Matsuoka, M Kuramitsu, Y Seki, T Mizukami, H Akari. Identification of natural remission of mother-to-child retroviral transmission. Journal of Infectious Diseases. 2025; in press.
  4. Y Iwatani, K Matsuoka, H Ode, M Kubota, Y Nakata, Y Setoyama, K Kojima, M Imahashi, Y Yokomaku. The unique structure of the highly conserved PPLP region in HIV-1 Vif is critical for the formation of APOBEC3 recognition interfaces. mBio. 2025; 16: e0333224.

• 2024

  1. H Ode, M Matsuda, U Shigemi, M Mori, Y Yamamura, Y Nakata, R Okazaki, M Kubota, Y Setoyama, M Imahashi, Y Yokomaku, Y Iwatani. Population-based nanopore sequencing of the HIV-1 pangenome to identify drug resistance mutations. Scientific Reports. 2024; 14:12099.
  2. M Aboshi, K Matsuda, D Kawakami, K Kono, Y Kazami, T Sekida, M Komori, A Morey, S Suga, J F Smith, T Fukuhara, Y Iwatani, Y Takahashi, T Yamamoto, N Sato, W Akahata. Safety and immunogenicity of VPLCOV-02, a SARS-CoV-2 self-amplifying RNA vaccine with a modified base, 5-methylcytosine, in healthy individuals. iScience. 2024; 27:108964.

• 2023

  1. Y Ito, H Lu, M Kitajima, H Ishikawa, Y Nakata, Y Iwatani, T Hoshino. Sticklac-derived natural compounds inhibiting RNase H activity of HIV-1 reverse transcriptase. Journal of Natural Products. 2023; 78: 2859-2868.
  2. S Uno, H Gatanaga, T Hayashida, M Imahashi, R Minami, M Koga, S Samukawa, D Watanabe, T Fujii, M Tateyama, H Nakamura, S Matsushita, Y Yoshino, T Endo, M Horiba, T Taniguchi, H Moro, T Igari, S Yoshida, T Teshima, H Nakajima, M Nishizawa, Y Yokomaku, Y Iwatani, A Hachiya, S Kato, N Hasegawa, K Yoshimura, W Sugiura, T Kikuchi, the Japanese Drug Resistance HIV-1 Surveillance Network. Virological outcomes of various first-line ART regimens in patients harboring HIV-1 E157Q integrase polymorphism: a multicenter retrospective study. Journal of Antimicrobial Chemotherapy. 2023; 86: 2487-2495.
  3. A Sugimoto, T Watanabe, K Matsuoka, Y Okuno, Y Yanagi, Y Narita, S Mabuchi, H Nobusue, E Sugihara, M Hirayama, T Ide, T Onouchi, Y Sato, T Kanda, H Saya, Y Iwatani, H Kimura, T Murata. Growth transformation of B cells by Epstein-Barr Virus requires IMPDH2 induction and nucleolar hypertrophy. Microbiology Spectrum. 2023; 11: e0044023.
  4. K Takamure, Y Iwatani, H Amano, T Yagi, T Uchiyama. Inactivation characteristics of a 280 nm deep-UV irradiation dose on aerosolized SARS-CoV-2. Environment International. 2023; 177:108022.
  5. W Akahata, T Sekida, T Nogimori, H Ode, T Tamura, K Kono, Y Kazami, A Washizaki, Y Masuta, R Suzuki, K Matsuda, M Komori, AL Morey, K Ishimoto, M Nakata, T Hasunuma, T Fukuhara, Y Iwatani, T Yamamoto, JF Smith, N Sato. Safety and immunogenicity of SARS-CoV-2 self-amplifying RNA vaccine expressing anchored RBD: a randomised, observer-blind, phase 1 study. Cell Reports Medicine. 2023; 4:101134.
  6. H Hamada, M Futamura, H Ito, R Yamamoto, K Yata, Y Iwatani, H Inoue, N Fukatsu, H Nagai, Y Hasegawa. Association of a third vaccination with antibody levels and side reactions in essential workers: a prospective cohort study. Vaccine. 2023; 41: 1632-1637.
  7. Y Nakata, H Ode, M Kubota, T Kasahara, K Matsuoka, A Sugimoto, M Imahashi, Y Yokomaku, Y Iwatani. The cellular APOBEC3A deaminase drives mutations in the SARS-CoV-2 genome. Nucleic Acids Research. 2023; 51:783-795.

• 2022

  1. K Takamure, Y Sakamoto, Y Iwatani, H Amano, T Yagi, T Uchiyama. Characteristics of collection and inactivation of virus in air flowing inside a winding conduit equipped with 280 nm deep UV-LEDs. Environment International. 2022;170: 107580.
  2. TS Tan, M Toyoda, H Ode, G Barabona, H Hamana, M Kitamatsu, H Kishi, C Motozono, Y Iwatani, T Ueno. Dissecting naturally arising amino acid substitutions at position L452 of SARS-CoV-2 Spike. Journal of Virology. 2022; 96:e01162-22.
  3. H Ode, A Saito, A Washizaki, Y Seki, T Yoshida, S Harada, H Ishii, T Shioda, Y Yasutomi, T Matano, T Miura, H Akari, Y Iwatani. Development of a novel macaque-tropic HIV-1 adapted to cynomolgus macaques. Journal of General Virology. 2022; 103:001790.
  4. M Mori, H Ode, M Kubota, Y Nakata, T Kasahara, U Shigemi, R Okazaki, M Matsuda, K Matsuoka, A Sugimoto, A Hachiya, M Imahashi, Y Yokomaku, Y Iwatani. Nanopore sequencing for characterization of HIV-1 recombinant forms. Microbiology Spectrum. 2022; 10: e0150722.
  5. U Shigemi, Y Yamamura, M Matsuda, R Okazaki, M Kubota, S Ibe, M Nemoto, M Maejima-Kitagawa, S Sukegawa, M Imahashi, T Kikuchi, W Sugiura, Y Iwatani, A Hachiya, Y Yokomaku, Japanese Drug Resistance HIV-1 Surveillance Network. Evaluation of the Geenius HIV 1/2 confirmatory assay for HIV-2 samples isolated in Japan. Journal of Clinical Virology. 2022; 152: 105189
  6. K Takamure, Y Sakamoto, T Yagi, Y Iwatani, H Amano, T Uchiyama. Blocking effect of desktop air curtain on aerosols in exhaled breath. AIP Advances. 2022; 12.055323.
  7. H Ode, Y Nakata, M Nagashima, M Hayashi, T Yamazaki, H Asakura, J Suzuki, M Kubota, K Matsuoka, M Matsuda, M Mori, A Sugimoto, M Imahashi, Y Yokomaku, K Sadamasu, Y Iwatani. Molecular-epidemiological features of SARS-CoV-2 in Japan, 2020-1. Virus Evolutions. 2022; 8: veac034.
  8. T Kondo, K Matsuoka, S Umemoto, T Fujino, G Hayashi, Y Iwatani, H Murakami. Monobodies with potent neutralizing activity against SARS-CoV-2 Delta and other variants of concern. Life Science Alliance. 2022; 5: e202101322.
  9. K Matsuoka, N Imahashi, M Ohno, H Ode, Y Nakata, M Kubota, A Sugimoto, M Imahashi, Y Yokomaku, Y Iwatani (selected as “Editor’s Picks). SARS-CoV-2 accessory protein ORF8 is secreted extracellularly as a glycoprotein homodimer. Journal of Biological Chemistry. 2022; 298: 101724.

• 2021

  1. T Kasahara, M Imahashi, C Hashiba, M Mori, A Kogure, Y Yokomaku, N Hashimoto, Y Iwatani, Hasegawa Y. Retrospective analysis of the efficacy of early antiretroviral therapy in HIV-1-infected patients coinfected with Pneumocystis jirovecii. AIDS Research and Human Retroviruses. 2021; 37: 754-760.
  2. A Sugimoto, Y Abe, T Watanabe, K Hosokawa, J Adachi, T Tomonaga, Y Iwatani, T Murata, M Fujimuro. The FAT10 post-translational modification is involved in the lytic replication of Kaposi's sarcoma-associated herpesvirus. Journal of Virology. 2021; 95: e02194-20.
  3. N Urata, T Watanabe, N Hirashima, Y Yokomaku, J Imamura, Y Iwatani, M Shimada, Y Tanaka. Cytokines and Chemokines Involved in Hepatitis B Surface Antigen Loss in Human Immunodeficiency Virus/Hepatitis B Virus Coinfected Patients. Journal of Clinical Microbiology. 2021; 10: 833.
  4. S Ozono, Y Zhang, H Ode, K Sano, TS Tan, K Imai, K Miyoshi, S Kishigami, T Ueno, Y Iwatani, T Suzuki, K Tokunaga. SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity. Nature Communications. 2021; 12:848.
  5. M Imahashi, H Ode, A Kobayashi, M Nemoto, M Matsuda, C Hashiba, A Hamano, Y Nakata, M Mori, K Seko, M Nakahata, A Kogure, Y Tanaka, W Sugiura, Y Yokomaku, Y Iwatani. Impact of long‑term antiretroviral therapy on gut and oral microbiotas in HIV‑1‑infected patients. Scientific Reports. 2021; 11: 910.

Research Keywords

AIDS, HIV, Infectious Diseases, Virus, Drug Resistance, Drug Discovery, APOBEC3, Cellular Defense Factors, Anti-viral

Others

We are interested in “epidemiology, retrovirology, structure biology, and basic sciences in HIV/AIDS and the related pathogens”. Our mission is to provide graduate students with the highest quality of research environment, and thereby to educate them to be scientists who can contribute international medical sciences. We welcome interested students with various backgrounds in the research major for their graduations. We hope many students to join in our group and to enjoy the research projects.You can access our lab website (https://nagoya.hosp.go.jp/crc/en/departments/infectious_diseases/).