学转换率的PEG-IFNα- 2a和恩替卡韦（ETV）联合和序贯治疗的Ⅳ

lifflefield

https://www.google.com/#hl=zh-CN&q=IFN++APOBEC3G+induce+HIV+hypermutation&oq=IFN++APOBEC3G+induce+HIV+hypermutation&aq=f&aqi=&aql=&gs_l=serp.3...3597l4198l2l4416l4l4l0l0l0l0l61l240l4l4l0.frgbld.&bav=on.2,or.r_gc.r_pw.,cf.osb&fp=628130d24ccc9543&biw=1498&bih=842

lifflefield

Role of retroviral restriction factors in the interferon-α–mediated ...
www.pnas.org/content/109/8/3035/F3.expansion.html - 翻译此页
21 Feb 2012
– APOBEC3-induced HIV-1 hypermutation during IFN-α/riba treatment. (干扰素引起APOBEC3家族带来HIV基因组高突变)
(A) Relationship between GG to AG (APOBEC3G dinucleotide context) ...

Dual effect of APOBEC3G on Hepatitis B - Journal of General Virology



vir.sgmjournals.org/content/88/2/432.full - 翻译此页
作者：C Noguchi - 2007 - 被引用次数：38  - 相关文章
Deamination-inactive APOBEC3G did not induce hypermutation, but reduced ... inducesG to A hypermutation to a nascent reverse transcript of HIV and serves as ... (2006) demonstrated that IFN induces transcription of APOBEC proteins and ...

lifflefield

干扰素已经不再是治疗乙肝的第一首选药物了，就是因为他带来的高病毒变异。 这些都是已经论证了5年的结论了。
不管是HIV还是HBV，干扰素刺激下，突变都是大幅增加的，以上的论文大家都可以一一查看，这种论文都会有几百篇了，不会少的。
请大家以后尽量第一选择用药，是核苷类药物

lifflefield

国内只有一片类似文章：
慢性乙型肝炎患者体内病毒基因G→A超突变的检测及分析
www.heporg.com/pnews/detail.asp?...ord... - 頁庫存檔 - 轉為繁體網頁。
抗病毒治疗是治疗慢性乙型肝炎和防止肝病进展的关键措施，一般包括干扰素治疗和核苷（酸）类似物治疗。国外有报道用干扰素治疗后，HBV发生G→A超突变的频率明显提高，这可能与干扰素可诱导APOBEC3G的产生有关[3]。在本研究中我们观察到用阿德福韦酯治疗前后HBV发生G→A超突变的频率没有明显变化，这从另一方面也验证了核苷（酸）类似物和干扰素抗HBV的机制不一样。

StephenW

回复 lifflefield 的帖子

This is the discussion from the 2006 paper:
Dual effect of APOBEC3G on Hepatitis B virus                                 

• Chiemi Noguchi1,2,                     
• Nobuhiko Hiraga1,2,                     
• Nami Mori1,2,                     
• Masataka Tsuge1,2,                     
• Michio Imamura1,2,                     
• Shoichi Takahashi1,2,                     
• Yoshifumi Fujimoto2,3,                     
• Hidenori Ochi2,3,                     
• Hiromi Abe1,3,                     
• Toshiro Maekawa3,                     
• Hiromi Yatsuji1,4,                     
• Kotaro Shirakawa5,                     
• Akifumi Takaori-Kondo5 and                     
• Kazuaki Chayama1,2,3
  

"We also demonstrated that the number of hypermutated genomes increased with the expression of APOBEC3G and APOBEC3F (Fig. 8⇑), but not in deaminase-inactive mutants, as demonstrated previously in HIV studies (Shindo et al., 2003; Newman et al., 2005). However, these mutants also reduced the replication of HBV almost to the wild-type level. This suggests that the contribution  of hypermutation of HBV to the reduction of virus replication is only minimal and supports the previous report that showed  that APOBEC3G reduced the replication of HBV through inhibition of packaging of the pregenome (Turelli et al., 2004a). However, the effect of hypermutation on infectivity of the virus should be investigated further. The effects of APOBEC  proteins, including other family members, especially under physiological conditions, should also be examined further. Whether            any HBV protein inhibits deamination of the genomic DNA awaits further investigation. Furthermore, the mechanism that enables  HBV to cause chronic infection, especially escape from innate antiviral immunity, should also be clarified in order to control   chronic HBV infection and reduce HBV-related morbidity."

Where is the evidence that:
The mutants are more efficient in replication and will be selected to replace the wild type?

Interferons activate many genes and produce many proteins. So we need to consider the total effect, rather than just one aspect. Research suggested Interferons influence cccDNA epigenetically too.

希望奇迹

在实际生活中,使用干扰素有较多的条件限制,比如影响工作,影响生活,再加上副作用和疗效的不确定,因此让很多人走上了核苷之路.      赞成！我就是！

StephenW

回复 希望奇迹 的帖子


干扰素有利有弊, 副作用可管理的.

MP4

lifflefield 发表于 2012-3-22 23:33
Why？ 现在很多论文已经不止一次的探讨了这个问题： 那么我再次强调一下：     干扰素，刺激细胞内源的， ...

你以为是抗病毒药的变异么?
这种变异会导致病毒神经衰弱的。