Viral Pathogenesis

小柳 Yoshio Koyanagi, M.D., Ph.D. Professor  btn

From retrovirus researches it has been achieved the discoveries of reverse transcriptase and retroviral oncogenes. It is clear that these discoveries provided strong advances on Virology and Cell Biology. Then, it has been well known that ‘‘retroviruses can cause some human diseases’’ after the discovery of human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV). We now know the importance of retrovirus research. Therefore, we believe that our efforts will contribute to Medical as well as Life Sciences.

Research and Education

Research projects have been arranged.

1) Replication of viral genome
Virus infects cell and replicates. Viral genome moves from virion-produced cell to adjacent naive cells. This is a most significant characteristic of virus. The mechanism of this infection event is a primary theme. The genome movement is not restricted in cell to cell infection. Inside cells, viral genomes or/and viral proteins move. Virus uses cellular trafficking machinery. We wish to learn the mechanism.

2) Regulation of HIV replication by host molecules
Virus cannot replicate without cells. Since it has been finding many essential and suppressive cellular factors on HIV replication, we wish to learn the mechanism of HIV replication from aspect of Immunology and Virology.

3) Mechanism of HIV pathogenesis
HIV causes immunodeficiency in human. The mechanism of the immunodeficiency remains unclear. It has been analyzing how the immunodeficiency occurs using in vitro-cell culture models and in vivo-animal models. We developed a mouse system that human immune system is transplanted in SCID mouse and in this human-chimera mouse abundant CD4 cell killing can be reproduced with HIV infection.

Fig. 1. Possible mechanism of adaptive evolution of SIVcpz to humans.

Fig. 2. HIV-1s co-infection into stable A3H humanized mouse.


Recent Publications

  1. Sato K, Misawa N, Takeuchi JS, Kobayashi T, Izumi T, Aso H, Nagaoka S, Yamamoto K, Kimura I, Yoriyuki Konno Y, Nakano Y, Koyanagi Y. Experimental adaptive evolution of simian immunodeficiency virus SIVcpz to pandemic human immunodeficiency virus type 1 using a humanized mouse model. J. Virol, 92, e01905-17, 2018.
  2. Soper A, Kimura I, Nagaoka S, Konno Y, Yamamoto K, Koyanagi Y, Sato K. Type I Interferon Responses by HIV-1 Infection: Association with Disease Progression and Control. Front Immunol. 8:1823, 2018.
  3. Yamada E, Nakaoka S, Klein L, Reith E, Langer S, Hopfensperger K, Iwami S, Schreiber G, Kirchhoff F, Koyanagi Y, Sauter D, Sato K. Human-specific adaptations in Vpu conferring anti-tetherin activity are critical for efficient early HIV-1 replication in vivo. Cell Host Microbe 23:110-120, 2018.
  4. Nakano Y, Misawa N, Juarez-Fernandez G, Moriwaki M, Nakaoka S, Funo T, Yamada E, Soper A, Yoshikawa R, Ebrahimi D, Tachiki Y, Iwami S, Harris RS, Koyanagi Y, Sato K. HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation. PLoS Pathog. 13:e1006348, 2017.
  5. Iwami S, Takeuchi JS, Nakaoka S, Mammano F, Clavel F, Inaba H, Kobayashi T, Misawa N, Aihara K, Koyanagi Y, Sato K. (2015) Cell-to-cell infection by HIV contributes over half of virus infection. eLife 4:e08150.

Laboratory

Laboratory of Systems Virology, Department of Biosystems Science
Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
Professor : Yoshio Koyanagi. MD
Assistant Professor : Yusuke Nakano, Ph. D
Assistant Professor : Yuki Furuse. MD
TEL : +81-75-751-4813
FAX : +81-75-751-4812
e-mail : virus@pathohotmail.com
URL : http://www.infront.kyoto-u.ac.jp/ex_ivr/Lab/KoyanagiHP/