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标题: 丁型肝炎：揭示了病毒生命周期的奥秘 [打印本页]

作者: StephenW 时间: 2019-12-20 20:17 标题: 丁型肝炎：揭示了病毒生命周期的奥秘

Hepatitis D: The mystery of the virus' life cycle revealed

Professor Patrick Labonté's team at the INRS reveals the key role of a cellular process in the development of the Hepatitis D virus

Institut national de la recherche scientifique - INRS

IMAGE: Hepatitis D virus replication (red) induces autophagy (green) in the host cell (fluorescence microscopy). view more

Credit: Patrick Labonté, INRS

      Montreal, December 19 2019-- A team led by Professor Patrick Labonté at the Institut National de la Recherche Scientifique (INRS) in Montreal, Canada has identified the role of a key process in the replication cycle of the hepatitis D virus, an infection that is still very difficult to cure and affects 15 to 20 million people worldwide.
      The hepatitis D virus (HVD) has a specific target: it infects only people carrying the hepatitis B virus (HBV). As with other co-infections, the combination of hepatitis B and D causes more liver damage than hepatitis B alone.
      "HDV needs HBV to survive, it's like a parasite," says researcher Patrick Labonté who specializes in liver viruses (hepatitis). However, cure rates are low because treatments for hepatitis B are ineffective against HDV."
      "It may seem contradictory since the virus cannot survive on its own," he adds. "In fact, drugs target a specific enzyme to control hepatitis B, but treatment does not completely eliminate the virus. The VHD survives normally and can continue its damage."
      The challenge for Professor Labonté and his research team is thus to find a treatment that will fight both viruses and it seems they are on the right track.
      In a study published recently in the Journal of Virology, the team showed that VHD was exploiting the same cellular protein as HBV, called ATG5, to promote its development, particularly its replication in the nucleus of the host cell. This protein is essential for what is called autophagy; a process that is used for cleaning cellular waste. In theory, autophagy should be able to destroy invaders, but most viruses, such as hepatitis C or influenza, have evolved to avoid this degradation and even use autophagy to their advantage.
      "Several studies have looked at the role of autophagy in viruses, but it varies from one virus to another depending on its replication process. We are the first to determine the effect of the process on the hepatitis D virus," says Professor Labonté, who is also the study's corresponding author. He was not surprised that ATG5 protein benefits these two hepatitis viruses since they are closely linked.
      Towards a Potential Treatment
      With this common protein, the autophagic process could be a solution since it is essential to the life cycle of these viruses. However, the situation is not that simple. "If we block autophagy, then we are blocking an important function for all cells in the body. We do not know what the long-term effects might be. Autophagy should be inhibited in a targeted and temporary manner," warns Patrick Labonté;.
      According to the World Health Organization, at least 5% of people with chronic HBV infection are also infected with HDV. HBV-HDV co-infection is the most severe form of chronic viral hepatitis because it progresses very quickly and can even be fatal. "Hepatitis B virus alone can cause cirrhosis or liver cancer. When combined with the hepatitis D virus, the development of these diseases happens more frequently and more rapidly," he says.
      In the course of this research, Professor Labonté;'s team made an interesting discovery: some autophagy proteins travel outside their usual area. "Autophagy usually occurs in the cell's cytoplasm, but the process contributes to the replication of the HDV genome which takes place in the nucleus. Are there any autophagic proteins present in the nucleus in the case of an infection?", wonders the researcher. This is an area that the team is currently studying and will hopefully provide a more in-depth understanding of the role of autophagy in HDV.

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      About the article
HDV alters the autophagy process to promote its genome replication by Marwa Khabir, Asma Zahra Aliche, Camille Sureau, Matthieu Blanchet, Patrick Labonté; was published in Journal of Virology. DOI: 10.1128/JVI.01936-19. This research was supported by funding from the Natural Sciences and Engineering Research Council of Canada (NSERC).
      About the INRS
The Institut national de la recherche scientifique (INRS) is the only institution in Québec dedicated exclusively to graduate-level university research and training. The impacts of its faculty and students are felt around the world. INRS proudly contributes to societal progress in partnership with industry and community stakeholders, both through its discoveries and by training new researchers and technicians to deliver scientific, social, and technological breakthroughs in the future.
      Media contact :
      Julie Robert
Communications, INRS
514 499-6603 (office)
514 971-4747 (cell)
[email protected]

作者: StephenW 时间: 2019-12-20 20:18

丁型肝炎：揭示了病毒生命周期的奥秘

INRS的PatrickLabonté教授的团队揭示了细胞过程在D型肝炎病毒发展中的关键作用

国家科学研究所
图片

图像：D型肝炎病毒复制（红色）在宿主细胞中诱导自噬（绿色）（荧光显微镜）。查看更多

图片提供：INRS的PatrickLabonté

2019年12月19日，蒙特利尔-由加拿大蒙特利尔国立科学研究所（INRS）的PatrickLabonté教授领导的团队确定了D型肝炎病毒复制周期中关键过程的作用，仍然很难治愈，并影响了全球15至2000万人。

丁型肝炎病毒（HVD）有一个特定的目标：它仅感染携带乙型肝炎病毒（HBV）的人。与其他合并感染一样，乙肝和丙肝的联合感染比单独的乙肝对肝脏的损害更大。

“ HDV需要HBV才能生存，就像寄生虫一样，”专门研究肝病毒（肝炎）的研究员PatrickLabonté说。但是，治愈率很低，因为乙型肝炎的治疗对HDV无效。 ”

他补充说：“这似乎是自相矛盾的，因为这种病毒无法独自生存。” “实际上，药物靶向一种特定的酶来控制乙型肝炎，但是治疗不能完全消除该病毒。VHD可以正常生存，并且可以继续造成损害。”

因此，Labonté教授及其研究团队面临的挑战是找到一种能同时对抗两种病毒的治疗方法，看来它们正在正确的轨道上。

在最近发表在《病毒学杂志》上的一项研究中，研究小组表明VHD正在利用与HBV相同的细胞蛋白ATG5来促进其发育，特别是其在宿主细胞核中的复制。这种蛋白质对于所谓的自噬至关重要。用于清洁细胞废物的过程。从理论上讲，自噬应该能够消灭入侵者，但是大多数病毒（例如丙型肝炎或流感病毒）已经进化以避免这种降解，甚至利用自噬发挥了优势。

Labonté教授说：“数项研究已经研究了自噬在病毒中的作用，但自噬在不同病毒之间又取决于其复制过程。我们是第一个确定该过程对D型肝炎病毒影响的人。”也是该研究的通讯作者。他不惊讶ATG5蛋白对这两种肝炎病毒有好处，因为它们密切相关。

寻求潜在的治疗

使用这种常见的蛋白质，自噬过程可能是一个解决方案，因为它对于这些病毒的生命周期至关重要。但是，情况并非如此简单。 “如果我们阻止自噬，那么我们正在阻断体内所有细胞的重要功能。我们不知道长期的影响是什么。应该以针对性和暂时的方式抑制自噬，” PatrickLabonté警告说。

根据世界卫生组织的数据，至少有5％的慢性HBV感染者也感染了HDV。 HBV-HDV合并感染是慢性病毒性肝炎的最严重形式，因为它进展非常迅速，甚至可能致命。他说：“仅乙型肝炎病毒就可以导致肝硬化或肝癌。当与乙型肝炎病毒结合使用时，这些疾病的发生更加频繁，更加迅速。”

在这项研究过程中，拉邦特教授的团队做出了一个有趣的发现：一些自噬蛋白在其通常区域之外传播。 “自噬通常发生在细胞的细胞质中，但是该过程有助于细胞核中HDV基因组的复制。如果发生感染，细胞核中是否存在自噬蛋白？”研究人员感到惊讶。该小组目前正在研究这一领域，并有望提供更深入的了解自噬在HDV中的作用。

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关于文章

HDV通过Marwa Khabir，Asma Zahra Aliche，Camille Sureau，Mattheu Blanchet，PatrickLabonté改变自噬过程以促进其基因组复制；发表在病毒学杂志上。 DOI：10.1128 / JVI.01936-19。这项研究得到了加拿大自然科学与工程研究委员会（NSERC）的资助。

关于INRS

国立科学研究所（INRS）是魁北克唯一一家专门研究研究生水平大学研究和培训的机构。它的教职员工和学生的影响力在世界各地都能感受到。 INRS通过其发现以及培训新的研究人员和技术人员，以在未来实现科学，社会和技术突破，与行业和社区利益相关者合作，为社会进步做出了令人自豪的贡献。

媒体联系：

朱莉·罗伯特
INRS通讯
514499-6603（办公室）
514 971-4747（单元格）
[email protected]

作者: 乐繁圆xwr 时间: 2020-5-31 00:01

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