http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485615/ Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.
【在 d**j 的大作中提到】 : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485615/ : Sodium taurocholate cotransporting polypeptide is a functional receptor for : human hepatitis B and D virus : Human hepatitis B virus (HBV) infection and HBV-related diseases remain a : major public health problem. Individuals coinfected with its satellite : hepatitis D virus (HDV) have more severe disease. Cellular entry of both : viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large : envelope protein is a key determinant for receptor(s) binding. However, the : identity of the receptor(s) is unknown. Here, by using near zero distance : photo-cross-linking and tandem affinity purification, we revealed that the
A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its position. 1. Only expressed NTCP in hepatocarcinoma cell which actually has been proved that can bind HBV and HDV( previously publication). Also some subtype of the hepatocarcinoma cell can be sensitive to HBV, which has been isolated by a German group. If using any other non-hepatocyte related cell would be much more convincing. 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV or HDV, it will definitely close the deal. It is not as good as HCV receptor papers, so I am not surprised it has been rejected by CNS. There are tons of papers claimed to find the HBV receptor, but none of them really provided solid evidences like HCV receptor did. Actually I feel a little disappointment.
for large the
【在 d**j 的大作中提到】 : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485615/ : Sodium taurocholate cotransporting polypeptide is a functional receptor for : human hepatitis B and D virus : Human hepatitis B virus (HBV) infection and HBV-related diseases remain a : major public health problem. Individuals coinfected with its satellite : hepatitis D virus (HDV) have more severe disease. Cellular entry of both : viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large : envelope protein is a key determinant for receptor(s) binding. However, the : identity of the receptor(s) is unknown. Here, by using near zero distance : photo-cross-linking and tandem affinity purification, we revealed that the
subtype Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Wenhui Li's paper about receptor of SRAS-Cov is published in Science, without any transgenic mouse model data.
【在 j*******n 的大作中提到】 : A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its : position. : 1. Only expressed NTCP in hepatocarcinoma cell which actually has been : proved that can bind HBV and HDV( previously publication). Also some subtype : of the hepatocarcinoma cell can be sensitive to HBV, which has been : isolated by a German group. If using any other non-hepatocyte related cell : would be much more convincing. : 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV : or HDV, it will definitely close the deal. : It is not as good as HCV receptor papers, so I am not surprised it has been
【在 j*******n 的大作中提到】 : A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its : position. : 1. Only expressed NTCP in hepatocarcinoma cell which actually has been : proved that can bind HBV and HDV( previously publication). Also some subtype : of the hepatocarcinoma cell can be sensitive to HBV, which has been : isolated by a German group. If using any other non-hepatocyte related cell : would be much more convincing. : 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV : or HDV, it will definitely close the deal. : It is not as good as HCV receptor papers, so I am not surprised it has been
1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Any other paper claimed to find HBV receptor also show data such like this paper. Non of them are convinced enough. Hepatocarcinoma cell can definitely bind the glycoprotein of HBV (tons of references) and some papers claimed that low percent of epatocarcinoma cell could be infected by HBV. It is looks like NTCP is just one of the co-receptors to enhance the infection but not the essential one. If such as 293T cell experssing NTCP could be infected by HBV, there will be no doubt. 2,Wenhui Li's paper about receptor of SRAS-Cov is published in Science, without any transgenic mouse model data. Different virus has different infection mechanism. Pleomorphic virus receptor usually is easy to be identified such as influenza virus, measles virus and SARS. And usually these virus' receptor includes only one or two proteins. Isocohedral virus's receptor such as HBV, alpha virus, flavivirus( HCV) are hard to say. Because during the infection, the whole virus has been going through significant rearrangement. Until now, only HCV virus receptor is much convincing and include several different proteins also has been successfully provided HCV sensitive transgenetic mouse. As I said, there are tons of paper claimed to find HBV receptor and published in JBC or JV. Scientist and company working in this field has been tired of so many false alarm. If it want to be superior, transgenic mouse model is essential.
1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Any other paper claimed to find HBV receptor also show data such like this paper. Non of them are convinced enough. Hepatocarcinoma cell can definitely bind the glycoprotein of HBV (tons of references) and some papers claimed that low percent of epatocarcinoma cell could be infected by HBV. It is looks like NTCP is just one of the co-receptors to enhance the infection but not the essential one. If such as 293T cell experssing NTCP could be infected by HBV, there will be no doubt. 对HBV了解不多,但是觉得你这个观点可能有点问题。HBV成功感染细胞并生存下来,可 能不只需要细胞表面受体,还会涉及到细胞内一些相应的通路吧。这些东西在肝细胞内 肯定是有了,但是在其它细胞,比如293T里面有没有?只表达一个表面受体能做到吗?
【在 j*******n 的大作中提到】 : 1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP : expression rendered nonsusceptible hepatocarcinoma cells susceptible to : these viral infections. : Any other paper claimed to find HBV receptor also show data such like this : paper. Non of them are convinced enough. Hepatocarcinoma cell can : definitely bind the glycoprotein of HBV (tons of references) and some papers : claimed that low percent of epatocarcinoma cell could be infected by HBV. : It is looks like NTCP is just one of the co-receptors to enhance the : infection but not the essential one. If such as 293T cell experssing NTCP : could be infected by HBV, there will be no doubt.
【在 Z******5 的大作中提到】 : : 1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP : expression rendered nonsusceptible hepatocarcinoma cells susceptible to : these viral infections. : Any other paper claimed to find HBV receptor also show data such like this : paper. Non of them are convinced enough. Hepatocarcinoma cell can : definitely bind the glycoprotein of HBV (tons of references) and some papers : claimed that low percent of epatocarcinoma cell could be infected by HBV. : It is looks like NTCP is just one of the co-receptors to enhance the : infection but not the essential one. If such as 293T cell experssing NTCP
【在 Z******5 的大作中提到】 : : 1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP : expression rendered nonsusceptible hepatocarcinoma cells susceptible to : these viral infections. : Any other paper claimed to find HBV receptor also show data such like this : paper. Non of them are convinced enough. Hepatocarcinoma cell can : definitely bind the glycoprotein of HBV (tons of references) and some papers : claimed that low percent of epatocarcinoma cell could be infected by HBV. : It is looks like NTCP is just one of the co-receptors to enhance the : infection but not the essential one. If such as 293T cell experssing NTCP
b*h
28 楼
那能用这个NTCP受体筛出控制乙肝病毒的拮抗剂阿。。
for large the
【在 d**j 的大作中提到】 : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485615/ : Sodium taurocholate cotransporting polypeptide is a functional receptor for : human hepatitis B and D virus : Human hepatitis B virus (HBV) infection and HBV-related diseases remain a : major public health problem. Individuals coinfected with its satellite : hepatitis D virus (HDV) have more severe disease. Cellular entry of both : viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large : envelope protein is a key determinant for receptor(s) binding. However, the : identity of the receptor(s) is unknown. Here, by using near zero distance : photo-cross-linking and tandem affinity purification, we revealed that the
o*d
29 楼
The paper claimed NTCP was functional receptor for HBV, but they did not claim it would be the only one. I believe there will be more proteins or molecules involved in HBV infection which are liver specific. Lots of papers in CNS reported that molecles in TLR7/8/9 pathway, RIG pathway and MAVs pathway etc are essential for virus infection, would you say all of those papers are not really solid or convincing? You can not solve all puzzles in one paper.
papers
【在 j*******n 的大作中提到】 : 1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP : expression rendered nonsusceptible hepatocarcinoma cells susceptible to : these viral infections. : Any other paper claimed to find HBV receptor also show data such like this : paper. Non of them are convinced enough. Hepatocarcinoma cell can : definitely bind the glycoprotein of HBV (tons of references) and some papers : claimed that low percent of epatocarcinoma cell could be infected by HBV. : It is looks like NTCP is just one of the co-receptors to enhance the : infection but not the essential one. If such as 293T cell experssing NTCP : could be infected by HBV, there will be no doubt.
j*n
30 楼
Science. 2005 Jul 22;309(5734):623-6. Epub 2005 Jun 9. Complete replication of hepatitis C virus in cell culture. Nature. 2007 Apr 12;446(7137):801-5. Epub 2007 Feb 25. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature. 2009 Feb 12;457(7231):882-6. Epub 2009 Jan 28. Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature. 2011 Jun 8;474(7350):208-11. doi: 10.1038/nature10168. A genetically humanized mouse model for hepatitis C virus infection. 请参看以上文献。
papers
【在 o**d 的大作中提到】 : The paper claimed NTCP was functional receptor for HBV, but they did not : claim it would be the only one. I believe there will be more proteins or : molecules involved in HBV infection which are liver specific. Lots of papers : in CNS reported that molecles in TLR7/8/9 pathway, RIG pathway and MAVs : pathway etc are essential for virus infection, would you say all of those : papers are not really solid or convincing? : You can not solve all puzzles in one paper. : : papers
【在 j*******n 的大作中提到】 : A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its : position. : 1. Only expressed NTCP in hepatocarcinoma cell which actually has been : proved that can bind HBV and HDV( previously publication). Also some subtype : of the hepatocarcinoma cell can be sensitive to HBV, which has been : isolated by a German group. If using any other non-hepatocyte related cell : would be much more convincing. : 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV : or HDV, it will definitely close the deal. : It is not as good as HCV receptor papers, so I am not surprised it has been
正是以前有很多的paper claim receptors 才导致这篇paper这么困难。 就像喊狼来了多了,等狼真的来了,反而将信将疑了。 我觉得大家应该期待一下李老师的后手 which are followed papers , animal models and therapetics drugs.
papers
【在 j*******n 的大作中提到】 : 1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP : expression rendered nonsusceptible hepatocarcinoma cells susceptible to : these viral infections. : Any other paper claimed to find HBV receptor also show data such like this : paper. Non of them are convinced enough. Hepatocarcinoma cell can : definitely bind the glycoprotein of HBV (tons of references) and some papers : claimed that low percent of epatocarcinoma cell could be infected by HBV. : It is looks like NTCP is just one of the co-receptors to enhance the : infection but not the essential one. If such as 293T cell experssing NTCP : could be infected by HBV, there will be no doubt.
【在 j*******n 的大作中提到】 : Science. 2005 Jul 22;309(5734):623-6. Epub 2005 Jun 9. : Complete replication of hepatitis C virus in cell culture. : Nature. 2007 Apr 12;446(7137):801-5. Epub 2007 Feb 25. : Claudin-1 is a hepatitis C virus co-receptor required for a late step in : entry. : Nature. 2009 Feb 12;457(7231):882-6. Epub 2009 Jan 28. : Human occludin is a hepatitis C virus entry factor required for infection of : mouse cells. : Nature. 2011 Jun 8;474(7350):208-11. doi: 10.1038/nature10168. : A genetically humanized mouse model for hepatitis C virus infection.
what I see are 4 CNS papers in 6 years, which exactly make my point: you can not solve all puzzles in one paper.
of
【在 j*******n 的大作中提到】 : Science. 2005 Jul 22;309(5734):623-6. Epub 2005 Jun 9. : Complete replication of hepatitis C virus in cell culture. : Nature. 2007 Apr 12;446(7137):801-5. Epub 2007 Feb 25. : Claudin-1 is a hepatitis C virus co-receptor required for a late step in : entry. : Nature. 2009 Feb 12;457(7231):882-6. Epub 2009 Jan 28. : Human occludin is a hepatitis C virus entry factor required for infection of : mouse cells. : Nature. 2011 Jun 8;474(7350):208-11. doi: 10.1038/nature10168. : A genetically humanized mouse model for hepatitis C virus infection.
j*n
39 楼
The HCV pseudo particles are based on the HIV budding system, not related to HCV budding system at all. HCV budding is a puzzle still.
【在 j*******n 的大作中提到】 : The HCV pseudo particles are based on the HIV budding system, not related to : HCV budding system at all. HCV budding is a puzzle still.
j*n
41 楼
Agree with u on HBV pseudo particles. No efficient HBV pseudo particles available right now. HDV probably is the only promising pseudo particles for HBV right now. However, HDV is not well studied and could only infected cell with the company of HBV. It is usually a lot of argument using such background unclear virus to generate pseudo particles to find receptor. When I heard the message of this paper, I thought they probably find a way to well generate the pseudo particles with a reporter system. I had too high expectation to this paper and result, just feel a little disappointment now. However it is indeed a really good job in the HBV field .
【在 j*******n 的大作中提到】 : Agree with u on HBV pseudo particles. No efficient HBV pseudo particles : available right now. HDV probably is the only promising pseudo particles for : HBV right now. However, HDV is not well studied and could only infected : cell with the company of HBV. It is usually a lot of argument using such : background unclear virus to generate pseudo particles to find receptor. : When I heard the message of this paper, I thought they probably find a way : to well generate the pseudo particles with a reporter system. : I had too high expectation to this paper and result, just feel a little : disappointment now. However it is indeed a really good job in the HBV field : .
1. NTCP是coreceptor,需要其它receptor。HBV/HDV复制需要hepatocytic cytosolic component,293估计不行。 2. 文章有人scoop。李文章出来几个小时,一个lab就寄来祝贺,并附上两篇in press paper,方法不同,结论相同,也是找到NTCP。 我觉得close the deal可以慢慢来,establish the lead是首要任务。一个KI至少大半 年,拿一个六年的工作去赌,要是最后就差几天,不太值得。
subtype been
【在 j*******n 的大作中提到】 : A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its : position. : 1. Only expressed NTCP in hepatocarcinoma cell which actually has been : proved that can bind HBV and HDV( previously publication). Also some subtype : of the hepatocarcinoma cell can be sensitive to HBV, which has been : isolated by a German group. If using any other non-hepatocyte related cell : would be much more convincing. : 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV : or HDV, it will definitely close the deal. : It is not as good as HCV receptor papers, so I am not surprised it has been
j*x
46 楼
2里面说的Heidelberg的Stephan Urban组吗? 纯好奇,呵呵
cytosolic press
【在 h******e 的大作中提到】 : 1. NTCP是coreceptor,需要其它receptor。HBV/HDV复制需要hepatocytic cytosolic : component,293估计不行。 : 2. 文章有人scoop。李文章出来几个小时,一个lab就寄来祝贺,并附上两篇in press : paper,方法不同,结论相同,也是找到NTCP。 : 我觉得close the deal可以慢慢来,establish the lead是首要任务。一个KI至少大半 : 年,拿一个六年的工作去赌,要是最后就差几天,不太值得。 : : subtype : been
o*8
47 楼
我来评价一下elife 这个杂志: 好吧。本来只是表达一下疑惑,没有兴趣研究这个杂志的。既然有如此强烈的呻吟,我 就take the opportunity 把elife 这个杂志好好研究了一下。 这里是senior editorial leadership的链接: http://www.elifesciences.org/about/elife-community/editorial-le 这里是Reviewing editor的链接: http://www.elifesciences.org/about/elife-community/reviewing-ed 阵容无疑是强大的,HHMI 嘛。 要命的是它的review process: http://www.elifesciences.org/the-journal/review-process/ 1. Our senior editors decide within a few days if the submission is appropriate for in-depth peer review. 2. The senior editors assign a member of the Board of Reviewing Editors to oversee the review process. The reviewing editor will usually review the article him or herself, as well – calling on additional external reviewers to join the conversation as needed. 资深编辑从杂志评审编辑中指派一人监督评审程序。该评审编辑通常也会参加评审- 如 果需要,也会从外部邀请评审参与。 3.Reviewers get together online to discuss their recommendations 评审在网上讨论推荐意见。 4.Further rounds of revision will be largely eliminated, as the reviewing editor will be able to assess most revised submissions without further outside review. 进一步评审通常没有必要,因为指派的评审编辑有能力评价大部分的修改稿件,无需进 一步评审。 5.We’ll post the decision letter and author responses 第2-4步是totally bullshit.这是我的reasoning: 理由1: 同行评议(peer review)的目的,就是能让做相同行业,有相关背景及经验 的专家来评价这个工作。所有严谨的科学杂志,都是要找相同专题的同行来评价投稿的 工作的。评审编辑可以是享誉盛名的学科领袖,可以是HHMI,甚至可以是诺贝尔奖得主 ,这都没有问题, 很好。可是如果你要是告诉我,这个杂志评审编辑board有能力评价 所有生命科技主题,我的回馈是:bullshit; 理由2:如果你要是告诉我,评审编辑board的牛人,全部都要commit to careful review of each submitted manuscript THEMSELVES, 我的回馈是:bullshit; 理由3:第4步就更可笑了。无需进一步评审?Are you kidding me? 以上分析,只是验证我原来的一个想法,elife这个杂志,只是HHMI 快速发表小圈子内 杂志,自娱自乐,相互意淫的一个平台而已。跟 PNAS 的科学院院士推荐发表如出一辙 。我就在这里大胆预测:elife这个杂志不会比 PNAS 走得更远,it will be a toy, that's all.
哈哈哈, and you are absolutely sure you mean what you are talking about? "其实elife不需要二轮评审的主要原因是大家都觉得revision过程太繁琐了" -太精屁了,我的倾佩之情,正如滚滚长江东逝水,又如无边落木萧萧下, 一发不可收 拾啊。
【在 o*******8 的大作中提到】 : 哈哈哈, : and you are absolutely sure you mean what you are talking about? : "其实elife不需要二轮评审的主要原因是大家都觉得revision过程太繁琐了" : -太精屁了,我的倾佩之情,正如滚滚长江东逝水,又如无边落木萧萧下, 一发不可收 : 拾啊。 : : subfield
没错,我招人确实要看文章以及发表在哪儿的,但我不是HR。我对文章的评价,首先 是看杂志名字,然后再看文章题目,然后再看abstract, 然后再看methods, 最后再看 conclusion. Of course that's just me. I am only a learning student. Review process的问题,不应该通过发明一个更 shitty的系统来解决。elife 就是那个更shitty的系统. 你有时间的话,我建议你看看这部电影: http://www.imdb.com/title/tt1645170/
【在 j*******n 的大作中提到】 : A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its : position. : 1. Only expressed NTCP in hepatocarcinoma cell which actually has been : proved that can bind HBV and HDV( previously publication). Also some subtype : of the hepatocarcinoma cell can be sensitive to HBV, which has been : isolated by a German group. If using any other non-hepatocyte related cell : would be much more convincing. : 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV : or HDV, it will definitely close the deal. : It is not as good as HCV receptor papers, so I am not surprised it has been
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485615/ Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.
f*n
73 楼
搬个小板凳,坐等评论。
E*2
74 楼
zan!! zan!! zan!!
for large the
【在 d**j 的大作中提到】 : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485615/ : Sodium taurocholate cotransporting polypeptide is a functional receptor for : human hepatitis B and D virus : Human hepatitis B virus (HBV) infection and HBV-related diseases remain a : major public health problem. Individuals coinfected with its satellite : hepatitis D virus (HDV) have more severe disease. Cellular entry of both : viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large : envelope protein is a key determinant for receptor(s) binding. However, the : identity of the receptor(s) is unknown. Here, by using near zero distance : photo-cross-linking and tandem affinity purification, we revealed that the
l*o
75 楼
Data are solid and convincing. Well done!
j*n
76 楼
A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its position. 1. Only expressed NTCP in hepatocarcinoma cell which actually has been proved that can bind HBV and HDV( previously publication). Also some subtype of the hepatocarcinoma cell can be sensitive to HBV, which has been isolated by a German group. If using any other non-hepatocyte related cell would be much more convincing. 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV or HDV, it will definitely close the deal. It is not as good as HCV receptor papers, so I am not surprised it has been rejected by CNS. There are tons of papers claimed to find the HBV receptor, but none of them really provided solid evidences like HCV receptor did. Actually I feel a little disappointment.
for large the
【在 d**j 的大作中提到】 : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485615/ : Sodium taurocholate cotransporting polypeptide is a functional receptor for : human hepatitis B and D virus : Human hepatitis B virus (HBV) infection and HBV-related diseases remain a : major public health problem. Individuals coinfected with its satellite : hepatitis D virus (HDV) have more severe disease. Cellular entry of both : viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large : envelope protein is a key determinant for receptor(s) binding. However, the : identity of the receptor(s) is unknown. Here, by using near zero distance : photo-cross-linking and tandem affinity purification, we revealed that the
o*d
77 楼
subtype Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Wenhui Li's paper about receptor of SRAS-Cov is published in Science, without any transgenic mouse model data.
【在 j*******n 的大作中提到】 : A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its : position. : 1. Only expressed NTCP in hepatocarcinoma cell which actually has been : proved that can bind HBV and HDV( previously publication). Also some subtype : of the hepatocarcinoma cell can be sensitive to HBV, which has been : isolated by a German group. If using any other non-hepatocyte related cell : would be much more convincing. : 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV : or HDV, it will definitely close the deal. : It is not as good as HCV receptor papers, so I am not surprised it has been
w*e
78 楼
一旦启动提交,并被审阅 这些实验谁敢在一篇文章做完,被scoop的风险太大了
subtype been
【在 j*******n 的大作中提到】 : A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its : position. : 1. Only expressed NTCP in hepatocarcinoma cell which actually has been : proved that can bind HBV and HDV( previously publication). Also some subtype : of the hepatocarcinoma cell can be sensitive to HBV, which has been : isolated by a German group. If using any other non-hepatocyte related cell : would be much more convincing. : 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV : or HDV, it will definitely close the deal. : It is not as good as HCV receptor papers, so I am not surprised it has been
j*n
79 楼
1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Any other paper claimed to find HBV receptor also show data such like this paper. Non of them are convinced enough. Hepatocarcinoma cell can definitely bind the glycoprotein of HBV (tons of references) and some papers claimed that low percent of epatocarcinoma cell could be infected by HBV. It is looks like NTCP is just one of the co-receptors to enhance the infection but not the essential one. If such as 293T cell experssing NTCP could be infected by HBV, there will be no doubt. 2,Wenhui Li's paper about receptor of SRAS-Cov is published in Science, without any transgenic mouse model data. Different virus has different infection mechanism. Pleomorphic virus receptor usually is easy to be identified such as influenza virus, measles virus and SARS. And usually these virus' receptor includes only one or two proteins. Isocohedral virus's receptor such as HBV, alpha virus, flavivirus( HCV) are hard to say. Because during the infection, the whole virus has been going through significant rearrangement. Until now, only HCV virus receptor is much convincing and include several different proteins also has been successfully provided HCV sensitive transgenetic mouse. As I said, there are tons of paper claimed to find HBV receptor and published in JBC or JV. Scientist and company working in this field has been tired of so many false alarm. If it want to be superior, transgenic mouse model is essential.
s*r
80 楼
这些实验不可能没做吧,NIBS的人力物力,一个转基因老鼠还不是手到擒来。
一旦启动提交,并被审阅 这些实验谁敢在一篇文章做完,被scoop的风险太大了 subtype been
1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Any other paper claimed to find HBV receptor also show data such like this paper. Non of them are convinced enough. Hepatocarcinoma cell can definitely bind the glycoprotein of HBV (tons of references) and some papers claimed that low percent of epatocarcinoma cell could be infected by HBV. It is looks like NTCP is just one of the co-receptors to enhance the infection but not the essential one. If such as 293T cell experssing NTCP could be infected by HBV, there will be no doubt. 对HBV了解不多,但是觉得你这个观点可能有点问题。HBV成功感染细胞并生存下来,可 能不只需要细胞表面受体,还会涉及到细胞内一些相应的通路吧。这些东西在肝细胞内 肯定是有了,但是在其它细胞,比如293T里面有没有?只表达一个表面受体能做到吗?
【在 j*******n 的大作中提到】 : 1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP : expression rendered nonsusceptible hepatocarcinoma cells susceptible to : these viral infections. : Any other paper claimed to find HBV receptor also show data such like this : paper. Non of them are convinced enough. Hepatocarcinoma cell can : definitely bind the glycoprotein of HBV (tons of references) and some papers : claimed that low percent of epatocarcinoma cell could be infected by HBV. : It is looks like NTCP is just one of the co-receptors to enhance the : infection but not the essential one. If such as 293T cell experssing NTCP : could be infected by HBV, there will be no doubt.
a*n
82 楼
表达到293T上至少可以做病毒结合试验吧?
papers
【在 Z******5 的大作中提到】 : : 1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP : expression rendered nonsusceptible hepatocarcinoma cells susceptible to : these viral infections. : Any other paper claimed to find HBV receptor also show data such like this : paper. Non of them are convinced enough. Hepatocarcinoma cell can : definitely bind the glycoprotein of HBV (tons of references) and some papers : claimed that low percent of epatocarcinoma cell could be infected by HBV. : It is looks like NTCP is just one of the co-receptors to enhance the : infection but not the essential one. If such as 293T cell experssing NTCP
【在 Z******5 的大作中提到】 : : 1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP : expression rendered nonsusceptible hepatocarcinoma cells susceptible to : these viral infections. : Any other paper claimed to find HBV receptor also show data such like this : paper. Non of them are convinced enough. Hepatocarcinoma cell can : definitely bind the glycoprotein of HBV (tons of references) and some papers : claimed that low percent of epatocarcinoma cell could be infected by HBV. : It is looks like NTCP is just one of the co-receptors to enhance the : infection but not the essential one. If such as 293T cell experssing NTCP
b*h
84 楼
那能用这个NTCP受体筛出控制乙肝病毒的拮抗剂阿。。
for large the
【在 d**j 的大作中提到】 : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485615/ : Sodium taurocholate cotransporting polypeptide is a functional receptor for : human hepatitis B and D virus : Human hepatitis B virus (HBV) infection and HBV-related diseases remain a : major public health problem. Individuals coinfected with its satellite : hepatitis D virus (HDV) have more severe disease. Cellular entry of both : viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large : envelope protein is a key determinant for receptor(s) binding. However, the : identity of the receptor(s) is unknown. Here, by using near zero distance : photo-cross-linking and tandem affinity purification, we revealed that the
o*d
85 楼
The paper claimed NTCP was functional receptor for HBV, but they did not claim it would be the only one. I believe there will be more proteins or molecules involved in HBV infection which are liver specific. Lots of papers in CNS reported that molecles in TLR7/8/9 pathway, RIG pathway and MAVs pathway etc are essential for virus infection, would you say all of those papers are not really solid or convincing? You can not solve all puzzles in one paper.
papers
【在 j*******n 的大作中提到】 : 1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP : expression rendered nonsusceptible hepatocarcinoma cells susceptible to : these viral infections. : Any other paper claimed to find HBV receptor also show data such like this : paper. Non of them are convinced enough. Hepatocarcinoma cell can : definitely bind the glycoprotein of HBV (tons of references) and some papers : claimed that low percent of epatocarcinoma cell could be infected by HBV. : It is looks like NTCP is just one of the co-receptors to enhance the : infection but not the essential one. If such as 293T cell experssing NTCP : could be infected by HBV, there will be no doubt.
j*n
86 楼
Science. 2005 Jul 22;309(5734):623-6. Epub 2005 Jun 9. Complete replication of hepatitis C virus in cell culture. Nature. 2007 Apr 12;446(7137):801-5. Epub 2007 Feb 25. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature. 2009 Feb 12;457(7231):882-6. Epub 2009 Jan 28. Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature. 2011 Jun 8;474(7350):208-11. doi: 10.1038/nature10168. A genetically humanized mouse model for hepatitis C virus infection. 请参看以上文献。
papers
【在 o**d 的大作中提到】 : The paper claimed NTCP was functional receptor for HBV, but they did not : claim it would be the only one. I believe there will be more proteins or : molecules involved in HBV infection which are liver specific. Lots of papers : in CNS reported that molecles in TLR7/8/9 pathway, RIG pathway and MAVs : pathway etc are essential for virus infection, would you say all of those : papers are not really solid or convincing? : You can not solve all puzzles in one paper. : : papers
【在 j*******n 的大作中提到】 : A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its : position. : 1. Only expressed NTCP in hepatocarcinoma cell which actually has been : proved that can bind HBV and HDV( previously publication). Also some subtype : of the hepatocarcinoma cell can be sensitive to HBV, which has been : isolated by a German group. If using any other non-hepatocyte related cell : would be much more convincing. : 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV : or HDV, it will definitely close the deal. : It is not as good as HCV receptor papers, so I am not surprised it has been
正是以前有很多的paper claim receptors 才导致这篇paper这么困难。 就像喊狼来了多了,等狼真的来了,反而将信将疑了。 我觉得大家应该期待一下李老师的后手 which are followed papers , animal models and therapetics drugs.
papers
【在 j*******n 的大作中提到】 : 1,Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP : expression rendered nonsusceptible hepatocarcinoma cells susceptible to : these viral infections. : Any other paper claimed to find HBV receptor also show data such like this : paper. Non of them are convinced enough. Hepatocarcinoma cell can : definitely bind the glycoprotein of HBV (tons of references) and some papers : claimed that low percent of epatocarcinoma cell could be infected by HBV. : It is looks like NTCP is just one of the co-receptors to enhance the : infection but not the essential one. If such as 293T cell experssing NTCP : could be infected by HBV, there will be no doubt.
【在 j*******n 的大作中提到】 : Science. 2005 Jul 22;309(5734):623-6. Epub 2005 Jun 9. : Complete replication of hepatitis C virus in cell culture. : Nature. 2007 Apr 12;446(7137):801-5. Epub 2007 Feb 25. : Claudin-1 is a hepatitis C virus co-receptor required for a late step in : entry. : Nature. 2009 Feb 12;457(7231):882-6. Epub 2009 Jan 28. : Human occludin is a hepatitis C virus entry factor required for infection of : mouse cells. : Nature. 2011 Jun 8;474(7350):208-11. doi: 10.1038/nature10168. : A genetically humanized mouse model for hepatitis C virus infection.
what I see are 4 CNS papers in 6 years, which exactly make my point: you can not solve all puzzles in one paper.
of
【在 j*******n 的大作中提到】 : Science. 2005 Jul 22;309(5734):623-6. Epub 2005 Jun 9. : Complete replication of hepatitis C virus in cell culture. : Nature. 2007 Apr 12;446(7137):801-5. Epub 2007 Feb 25. : Claudin-1 is a hepatitis C virus co-receptor required for a late step in : entry. : Nature. 2009 Feb 12;457(7231):882-6. Epub 2009 Jan 28. : Human occludin is a hepatitis C virus entry factor required for infection of : mouse cells. : Nature. 2011 Jun 8;474(7350):208-11. doi: 10.1038/nature10168. : A genetically humanized mouse model for hepatitis C virus infection.
j*n
95 楼
The HCV pseudo particles are based on the HIV budding system, not related to HCV budding system at all. HCV budding is a puzzle still.
【在 j*******n 的大作中提到】 : The HCV pseudo particles are based on the HIV budding system, not related to : HCV budding system at all. HCV budding is a puzzle still.
j*n
97 楼
Agree with u on HBV pseudo particles. No efficient HBV pseudo particles available right now. HDV probably is the only promising pseudo particles for HBV right now. However, HDV is not well studied and could only infected cell with the company of HBV. It is usually a lot of argument using such background unclear virus to generate pseudo particles to find receptor. When I heard the message of this paper, I thought they probably find a way to well generate the pseudo particles with a reporter system. I had too high expectation to this paper and result, just feel a little disappointment now. However it is indeed a really good job in the HBV field .
【在 j*******n 的大作中提到】 : Agree with u on HBV pseudo particles. No efficient HBV pseudo particles : available right now. HDV probably is the only promising pseudo particles for : HBV right now. However, HDV is not well studied and could only infected : cell with the company of HBV. It is usually a lot of argument using such : background unclear virus to generate pseudo particles to find receptor. : When I heard the message of this paper, I thought they probably find a way : to well generate the pseudo particles with a reporter system. : I had too high expectation to this paper and result, just feel a little : disappointment now. However it is indeed a really good job in the HBV field : .
1. NTCP是coreceptor,需要其它receptor。HBV/HDV复制需要hepatocytic cytosolic component,293估计不行。 2. 文章有人scoop。李文章出来几个小时,一个lab就寄来祝贺,并附上两篇in press paper,方法不同,结论相同,也是找到NTCP。 我觉得close the deal可以慢慢来,establish the lead是首要任务。一个KI至少大半 年,拿一个六年的工作去赌,要是最后就差几天,不太值得。
subtype been
【在 j*******n 的大作中提到】 : A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its : position. : 1. Only expressed NTCP in hepatocarcinoma cell which actually has been : proved that can bind HBV and HDV( previously publication). Also some subtype : of the hepatocarcinoma cell can be sensitive to HBV, which has been : isolated by a German group. If using any other non-hepatocyte related cell : would be much more convincing. : 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV : or HDV, it will definitely close the deal. : It is not as good as HCV receptor papers, so I am not surprised it has been
j*x
102 楼
2里面说的Heidelberg的Stephan Urban组吗? 纯好奇,呵呵
cytosolic press
【在 h******e 的大作中提到】 : 1. NTCP是coreceptor,需要其它receptor。HBV/HDV复制需要hepatocytic cytosolic : component,293估计不行。 : 2. 文章有人scoop。李文章出来几个小时,一个lab就寄来祝贺,并附上两篇in press : paper,方法不同,结论相同,也是找到NTCP。 : 我觉得close the deal可以慢慢来,establish the lead是首要任务。一个KI至少大半 : 年,拿一个六年的工作去赌,要是最后就差几天,不太值得。 : : subtype : been
o*8
103 楼
我来评价一下elife 这个杂志: 好吧。本来只是表达一下疑惑,没有兴趣研究这个杂志的。既然有如此强烈的呻吟,我 就take the opportunity 把elife 这个杂志好好研究了一下。 这里是senior editorial leadership的链接: http://www.elifesciences.org/about/elife-community/editorial-le 这里是Reviewing editor的链接: http://www.elifesciences.org/about/elife-community/reviewing-ed 阵容无疑是强大的,HHMI 嘛。 要命的是它的review process: http://www.elifesciences.org/the-journal/review-process/ 1. Our senior editors decide within a few days if the submission is appropriate for in-depth peer review. 2. The senior editors assign a member of the Board of Reviewing Editors to oversee the review process. The reviewing editor will usually review the article him or herself, as well – calling on additional external reviewers to join the conversation as needed. 资深编辑从杂志评审编辑中指派一人监督评审程序。该评审编辑通常也会参加评审- 如 果需要,也会从外部邀请评审参与。 3.Reviewers get together online to discuss their recommendations 评审在网上讨论推荐意见。 4.Further rounds of revision will be largely eliminated, as the reviewing editor will be able to assess most revised submissions without further outside review. 进一步评审通常没有必要,因为指派的评审编辑有能力评价大部分的修改稿件,无需进 一步评审。 5.We’ll post the decision letter and author responses 第2-4步是totally bullshit.这是我的reasoning: 理由1: 同行评议(peer review)的目的,就是能让做相同行业,有相关背景及经验 的专家来评价这个工作。所有严谨的科学杂志,都是要找相同专题的同行来评价投稿的 工作的。评审编辑可以是享誉盛名的学科领袖,可以是HHMI,甚至可以是诺贝尔奖得主 ,这都没有问题, 很好。可是如果你要是告诉我,这个杂志评审编辑board有能力评价 所有生命科技主题,我的回馈是:bullshit; 理由2:如果你要是告诉我,评审编辑board的牛人,全部都要commit to careful review of each submitted manuscript THEMSELVES, 我的回馈是:bullshit; 理由3:第4步就更可笑了。无需进一步评审?Are you kidding me? 以上分析,只是验证我原来的一个想法,elife这个杂志,只是HHMI 快速发表小圈子内 杂志,自娱自乐,相互意淫的一个平台而已。跟 PNAS 的科学院院士推荐发表如出一辙 。我就在这里大胆预测:elife这个杂志不会比 PNAS 走得更远,it will be a toy, that's all.
【在 o*******8 的大作中提到】 : 哈哈哈, : and you are absolutely sure you mean what you are talking about? : "其实elife不需要二轮评审的主要原因是大家都觉得revision过程太繁琐了" : -太精屁了,我的倾佩之情,正如滚滚长江东逝水,又如无边落木萧萧下, 一发不可收 : 拾啊。 : : subfield
没错,我招人确实要看文章以及发表在哪儿的,但我不是HR。我对文章的评价,首先 是看杂志名字,然后再看文章题目,然后再看abstract, 然后再看methods, 最后再看 conclusion. Of course that's just me. I am only a learning student. Review process的问题,不应该通过发明一个更 shitty的系统来解决。elife 就是那个更shitty的系统. 你有时间的话,我建议你看看这部电影: http://www.imdb.com/title/tt1645170/
【在 j*******n 的大作中提到】 : A descent paper. But not reach to CNS level. PNAS or Plos Pathogen is its : position. : 1. Only expressed NTCP in hepatocarcinoma cell which actually has been : proved that can bind HBV and HDV( previously publication). Also some subtype : of the hepatocarcinoma cell can be sensitive to HBV, which has been : isolated by a German group. If using any other non-hepatocyte related cell : would be much more convincing. : 2. If there is tansgenetic mouse expressing human NTCP is sensitive to HBV : or HDV, it will definitely close the deal. : It is not as good as HCV receptor papers, so I am not surprised it has been