B형 및 D형 간염바이러스 수용체
Receptor for Hepatitis B and D Virus
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초록
HBV는 지금까지 인류에 많은 해를 가져다 준 바이러스이지만 발견된 후 약 30년간의 연구에 의해 지금은 매우 강력하고 다양한 항바이러스 치료제가 임상에 사용되고 있다. 그러나, 항바이러스제를 많이 사용함에 따라 그에 상응하는 다양한 약제 내성 HBV 돌연변이들이 증가하고 있는 실정이다. 이러한 내성 바이러스들을 효과적으로 치료하기 위해서는 현재의 polymerase 저해제인 핵산유도체 항바이러스제와는 별도로, 새로운 바이러스의 생활사를 표적으로 하는 다른 기전의 항바이러스제 개발이 절실하다. 이러한 수요에 부합하여현재 다른 곳을 타깃으로 하는 다양한 연구가 활발히 진행되고 있으며, 가장 강력한 타깃으로 부상하고 있는 것이 최근에발견된 HBV의 수용체인 NTCP의 저해제 연구이다. 이를 위해서는 100% 감염이 가능한 세포주나 마우스 모델의 개발이절실히 요구된다. 위에서 언급하였듯이, 마우스의 간세포에사람의 NTCP를 과발현 시켜도 바이러스는 들어가지 못하는것이 발견되었으며[36], 이는 아직까지 발견하지 못한 또 다른 숙주 인자가 HBV의 감염에 필수적으로 작용하고 있음을강력히 시사한다. 따라서, 향후 HBV의 공동수용체(coreceptor) 들을 발굴하고 이들을 이용하여 연구를 함으로써 HBV 수용체에 작용하는 새로운 치료제의 개발을 앞당길 수 있을 것으로 생각된다.
Abstract
Chronic hepatitis B affects 400 million people worldwide and is one of the leading causes of liver-related morbidity and mortality. All clinically available hepatitis B virus (HBV) drugs are nucleoside or nucleotide analogs that inhibit viral reverse transcriptase (RT) activity. Resistance to these HBV drugs has been widely reported, and is due to specific mutations in the viral RT domain. Therefore, the development of new, non-polymerase targeting anti-HBV agents is urgently needed. A potential drug target, the HBV receptor that mediates the viral entry process, has been recently identified using human primary hepatocytes, northern tree shrew (Tupaia belangeri) hepatocytes, and HepaRG cells. A transporter of bile acids, sodium taurocholate cotransporting polypeptide (NTCP), was identified as the receptor for HBV and hepatitis D virus, and the transport function of NTCP was correlated with HBV entry. Therefore, functional inhibitors of NTCP may inhibit HBV infection, and viral entry was blocked by several NTCP receptor- targeting compounds. The HBV receptor is an attractive target for development of entry inhibitors, and serves as a model for the mechanistic study of HBV entry and infection. This review will summarize the characteristics and clinical importance of NTCP, and will discuss the potential therapeutic use of NTCP inhibitors to prevent HBV entry.
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