Principal Investigator_A.Ryo

Virological and proteomic analysis of the human immunodeficiency virus infection for antiviral drug discovery

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Tomohiko Tamura
Professor, Immunology
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Our Aim

The molecular interactions between viral and host-cell proteins are vital to the efficient and persistent replication of a virus. We are investigating the cellular processes and pathways that are involved in the dynamic interplay between HIV (human immunodeficiency virus) and host systems based on post-translational modifications (PTMs) of viral proteins. Elucidation of these processes should provide further insight into the nature of HIV replication and pathogenesis, and should be useful in the development of new anti-viral drugs.

Background

By the end of 2009, 33 million people were living with HIV. Although the mortality associated with HIV-related diseases, such as AIDS, has significantly declined because of highly active antiretroviral therapy (HAART), this in turn has increased the risk of drug-resistant virus forms developing during the long-term management of infected patients. Hence, advances in our understanding of the molecular signature of HIV and how it causes diseases is essential for future drug discovery efforts against HIV/AIDS.

Research Overview

We will investigate the dynamic interactions between HIV and host proteins during the virus replication cycle. We will identify PTMs of viral proteins by host factors which may be crucial for virus replication and pathogenesis. Based on the new findings, we will develop new anti-viral drugs targeting virus-host protein interactions.

Achievements

We have screened anti-retroviral drugs targeting virushost protein interactions using a wheat cell-free protein production system. We have identified host kinases/ phosphatases responsible for the modification of HIV proteins. We have also developed a novel in vitro phenotypic assay that provides a rapid and reliable method for evaluating the drug-resistance of the HIV protease.

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