The roles of the pre-genomic RNA in Hepatitis B Virus nucleocapsid assembly.

乙型肝炎病毒是一种常见的人类感染，全世界有超过20亿人接触过该病毒。大多数人从这种感染中完全康复，但也有相当一部分人没有康复，成为病毒携带者，这种情况与后来致命的肝硬化和肝癌有关。据估计，每年约有100万人死于乙肝病毒感染。在发达的西方国家有一种有效的疫苗，但这在世界上许多地方是不够的，那里超过8%的人口可能是受感染的携带者。因此，有必要设计新的抗病毒药物来抑制HBV感染，特别是使病毒对免疫系统可见，以便将其从患者体内清除。这是我们应用程序的目标，它基于我们最近的一项发现，与以RNA作为基因组核酸的病毒组装病毒颗粒的方式有关。我们已经发现，它们在这些rna的序列和结构中编码了一个隐藏的指令手册，确保了传染性病毒粒子的快速有效组装。HBV是一种稍微不同寻常的病毒，因为它最初在RNA前基因组RNA周围组装，但后来将其转化为病毒颗粒内的双链DNA版本。在广泛的初步实验中，我们已经表明HBV可能包含相同类型的初始组装说明书。因此，应该有可能使用药物靶向这一过程。我们要求获得为期两年的资助，这将使我们能够更全面地研究这一机制，并开始筛选可能阻碍组装的配体（药物）类型。在其他病毒系统中，这类药物会导致部分组装，也就是说，它们会产生非传染性但高度免疫原性的病毒版本，很容易被免疫系统发现。我们在这里获得的信息将在未来与制药公司讨论开发新型抗hbv疗法时具有宝贵的价值。

Hepatitis B virus is a common infection in humans with over 2 billion people worldwide having been exposed to the virus. The majority of people recover fully from such infections but a significant minority do not, becoming carriers of the virus, a condition linked to later lethal cirrhosis and liver cancer. It is estimated that ~1 million people die every year as a result of HBV infection. In advanced western countries there is an effective vaccine, but this is not sufficient in many parts of the world where over 8% of the population may be infected carriers. As a result there is a need to devise novel anti-viral drugs that would inhibit HBV infections, and in particular render the virus visible to the immune system so that it can be cleared from patients. This is the goal of our application, which is based on a recent discovery we made relating to the way that such viruses having RNA as their genomic nucleic acid, assemble their viral particles. We have discovered that they encode a hidden instruction manual in the sequence and structure of these RNAs that ensures rapid and efficient assembly of infectious virions. HBV is a slightly unusual virus because it assembles initially around an RNA pregenomic RNA but later converts that to a double-stranded DNA version within the viral particle. In extensive preliminary experiments we have shown that HBV may well contain the same sort of instruction manual for its initial assembly. It should therefore be possible to target this process using drugs. We are asking for a two year pump-priming grant that will allow us to investigate this mechanism more comprehensively and begin to screen for the types of ligands (drugs) that could block assembly. In other viral systems, such drugs lead to partial assembly, that is they create non-infectious but highly immunogenic versions of the virus that are readily seen by the immune system. The information we gain here will be invaluable in future discussions with drug companies about developing novel anti-HBV therapy.