Gastroenterology · 2005
Mapping of the hepatitis B virus attachment site by use of infection-inhibiting preS1 lipopeptides and tupaia hepatocytes.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Glebe Dieter, Urban Stephan, Knoop Eva V, Cag Nilgün, Krass Peter, Grün Stefanie, Bulavaite Aiste, Sasnauskas Kestutis, Gerlich Wolfram H
Аннотация
BACKGROUND & AIMS: Studies on the early steps in the life cycle of hepatitis B virus have been hampered by the lack of readily available target cells. In this study, we mapped a defined virus attachment site to primary hepatocytes that is essential for infection.
METHODS: We used purified virus particles from human carrier plasma as an inoculum and primary cultures of tupaia hepatocytes as susceptible target cells and studied the inhibitory effect of amino-terminally acylated preS1-derived lipopeptides on infection interference.
RESULTS: Infectivity of virus could be blocked efficiently in this system by amino-terminally acylated peptides containing amino acids 2-18 from the preS1 domain. The addition of amino acids 28-48 enhanced the inhibitory capacity, whereas amino acids 49-78 did not contribute to inhibition. Myristoylated preS1 peptides 2-48 bound strongly to tupaia hepatocytes but not to nonhepatic cells or rodent hepatocytes and thereby inhibited infection even at concentrations of 1 nmol/L completely. Particles consisting only of the small hepatitis B surface protein-the active component of current hepatitis B vaccines-did not bind at all to tupaia hepatocytes, but the addition of the preS1 domain to the particles allowed binding.
CONCLUSIONS: The preS1 sequence 2-48 mediates attachment of the virus to its target cells, whereas the small surface protein seems to be involved in other steps. These findings indicate that the current subunit hepatitis B vaccines may be improved by the addition of distinct preS1 epitopes. Moreover, preS1 lipopeptides are promising candidates for specific antiviral therapy against hepatitis B infections.
METHODS: We used purified virus particles from human carrier plasma as an inoculum and primary cultures of tupaia hepatocytes as susceptible target cells and studied the inhibitory effect of amino-terminally acylated preS1-derived lipopeptides on infection interference.
RESULTS: Infectivity of virus could be blocked efficiently in this system by amino-terminally acylated peptides containing amino acids 2-18 from the preS1 domain. The addition of amino acids 28-48 enhanced the inhibitory capacity, whereas amino acids 49-78 did not contribute to inhibition. Myristoylated preS1 peptides 2-48 bound strongly to tupaia hepatocytes but not to nonhepatic cells or rodent hepatocytes and thereby inhibited infection even at concentrations of 1 nmol/L completely. Particles consisting only of the small hepatitis B surface protein-the active component of current hepatitis B vaccines-did not bind at all to tupaia hepatocytes, but the addition of the preS1 domain to the particles allowed binding.
CONCLUSIONS: The preS1 sequence 2-48 mediates attachment of the virus to its target cells, whereas the small surface protein seems to be involved in other steps. These findings indicate that the current subunit hepatitis B vaccines may be improved by the addition of distinct preS1 epitopes. Moreover, preS1 lipopeptides are promising candidates for specific antiviral therapy against hepatitis B infections.