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The new model of HIV entry -- The fusion with endosomal membrane--

2009-11-30 (Mon) 4:00p.m. - 5:00 p.m.

Lecture topic: The new model of HIV entry -- The fusion with endosomal membrane--

Lecturer:Dr. Kosuke Miyauchi, AIDS Research Center, National Institute of Infectious Diseases

 

Dr. Kosuke Miyauchi who has engaged in research about viral membrane fusion under Dr. Melikyan at University of Maryland will speak at this important seminar.

The conventional perception was viral cellular membrane fusion occurs at the time of infection by Human Immunodeficiency Virus (HIV) on the surface of a cell because it does not depend on pH. However, Dr. Miyauchi and Dr. Melikyan re-examined this conventional theory by conducting ingenious experiments visualizing membrane fusion. As a result, they obtained multiple data suggesting that HIV also involves fusion with endosomal membrane as pH-dependent viruses do, and this theory attracted attention as a theory contradicting the established theory.

Enveloped viruses including Human Immunodeficiency Virus (HIV) must fuse to cellular membrane to achieve their infection. The membrane fusion is mediated by the conformational change of viral envelope protein. In low pH-dependent viruses, low pH provokes this conformational change. These viruses utilize low pH environment in endosome to mediate membrane fusion. On the other hand, in low pH-independent viruses, the conformational change of envelope protein is triggered by the cognitive viral receptor binding. HIV is a low pH-independent virus and their viral receptors exist on cell surface. Thus, it has been thought that HIV fuse on cell surface in general. However, some reports suggest the involvement of endocytosis pathway in HIV infection. To examine where HIV fuse in (on), we measured the kinetics of HIV fusion in real time by two different methods. From both experiments, we obtained data that strongly suggest the HIV fusion in endosome. Moreover, endocytosis inhibitors also inhibit HIV fusion. We propose the model of HIV infection that HIV binds to receptors on cell surface and then enters into the cells by endocytosis to complete the membrane fusion. The HIV entry through endosome may affect efficiency of various anti-HIV drugs (e.g. fusion inhibitory peptides or neutralize antibodies).

Reference

  • Miyauchi, K., Kozlov, M. M., Melikyan, G. B. "Early steps of HIV-1 fusion define the sensitivity to inhibitory peptides that block 6-helix bundle formation." PLoS Pathogens 5(9): e1000585. 2009.
  • Miyauchi, K., Kim, Y., Latinovic, O., Morozov, V., Melikyan, G. B. "HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes." Cell 137(3): 433-444. 2009.

*Students enrolled in the master's course of Graduate School of Medicine can take these lectures for academic credit.

Date: 2009-11-30 (Mon) 4:00p.m. - 5:00 p.m.
Sponsored: Department of Viral Infection, Research Institute for Microbial Diseases
Venue: Taniguchi Memorial Hall, 1st floor, Integrated Biosciences Research Bldg.
Registration: Not necessary.
Contact: Dr. Jun-ichi Sakuragi, Department of Viral Infections
sakuragi@biken.osaka-u.ac.jp

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