病毒是如何躲避免疫系统而存在的(2005.4.26)

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Replicative Homeostasis: A New Hypothesis to Explain How Viruses Such as HIV, HCV and HBV Persist and Escape Immune Controls

This article offers a new hypothesis concerning the persistence of certain viruses such as HIV, HCV and HBV and how they escape control by the immune system. In 40 days it has become the most downloaded article ever published by Virology Journal, an "Open Access" journal published by BioMed Central. This means that anyone can read, without charge, the articles appearing in it as soon as they are published.

The article explains why RNA viruses like Hepatitis C, HIV, West Nile / Yellow Fever / SARS / Ebola, etc persist, and demonstrates a mechanism of genotype/species maintenance, and of generating escape mutants in response to immune and other pressures. It explains why interferon may fail in some cases of hepatitis C and also explains the mechanism of antibody mediated disease enhancement. It also implies novel treatments for West Nile / HCV (and HIV, HBV, etc) might be possible, and describes what form they might take.

Hepatitis C (HCV), hepatitis B (HBV), the human immunodeficiency viruses (HIV), and other viruses that replicate via RNA intermediaries, cause an enormous burden of disease and premature death worldwide.

These viruses circulate within infected hosts as vast populations of closely related, but genetically diverse, molecules known as "quasispecies". The mechanism(s) by which this extreme genetic and antigenic diversity is stably maintained are unclear, but are fundamental to understanding viral persistence and pathobiology. The persistence of HCV, an RNA virus, is especially problematic and HCV stability, maintained despite rapid genomic mutation, is highly paradoxical.

This paper presents the hypothesis, and evidence, that viruses capable of persistent infection autoregulate replication and the likely mechanism mediating autoregulation--Replicative Homeostasis--is described.

Replicative homeostasis causes formation of stable, but highly reactive, equilibria that drive quasispecies expansion and generates escape mutation. Replicative homeostasis explains both viral kinetics and the enigma of RNA quasispecies stability and provides a rational, mechanistic basis for all observed viral behaviours and host responses.

More importantly, this paradigm has specific therapeutic implication and defines, precisely, new approaches to antiviral therapy. Replicative homeostasis may also modulate cellular gene expression.

Note: This article uses highly technical language that many readers will find difficult to follow at times. Although the language is challenging for non scientists, it is worth the effort to read through the entire article, which offers compelling insights into the possible mechanisms of how HIV, HCV and HBV, among other viruses, persist.

Link to complete text online

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reference R Sallie. Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation. Virology Journal 2(1):10. February 11, 2005

特深沉

病毒是如何躲避免疫系统而存在的(2005.4.26)

Replicative Homeostasis: A New Hypothesis to Explain How Viruses Such as HIV, HCV and HBV Persist and Escape Immune Controls

复制的动态平衡：一种新的假说，解释类似HIV,HBV,HBC等病毒，如何持续存在和躲

避免疫系统。

This article offers a new hypothesis concerning the persistence of certain viruses such as HIV, HCV and HBV and how they escape control by the immune system. In 40 days it has become the most downloaded article ever published by Virology Journal, an "Open Access" journal published by BioMed Central. This means that anyone can read, without charge, the articles appearing in it as soon as they are published.

本文提出了一个新的假说，关于类似HIV,HCV,HBV等病毒的持续存在，以及他们怎样

躲避免疫系统的控制。在过去的40天里，这是《病毒学杂志》发表的文章中被下载最

多的文章。（《病毒学杂志》是由BioMed Central发行的可公开获得的期刊。这意味着每

个人都可以免费阅读在这里发表的那些文章。）

The article explains why RNA viruses like Hepatitis C, HIV, West Nile / Yellow Fever / SARS / Ebola, etc persist, and demonstrates a mechanism of genotype/species maintenance, and of generating escape mutants in response to immune and other pressures. It explains why interferon may fail in some cases of hepatitis C and also explains the mechanism of antibody mediated disease enhancement. It also implies novel treatments for West Nile / HCV (and HIV, HBV, etc) might be possible, and describes what form they might take.

该文章解释了为什么RN病毒，像HCV, HIV, 西尼罗病毒/黄热病/SARS/埃博拉病毒，

等等，如何持续存在，论证了一种基因型/物种机制；因应免疫和其他压力而产生逃避

突变。这解释了为什么干扰素会在很多HCV病例中失败，还解释了抗体增进疾病的机

制。该文还提示针对西尼罗病毒/HCV/HIV/HBV等疾病新颖的治疗方法是可能的，并描

述了可能采用的形式。

Hepatitis C (HCV), hepatitis B (HBV), the human immunodeficiency viruses (HIV), and other viruses that replicate via RNA intermediaries, cause an enormous burden of disease and premature death worldwide.

HCV，HBC, HIV，和其他通过RNA复制为中介的病毒，在全世界造成了巨大的疾病

负担和过早死亡

These viruses circulate within infected hosts as vast populations of closely related, but genetically diverse, molecules known as "quasispecies". The mechanism(s) by which this extreme genetic and antigenic diversity is stably maintained are unclear, but are fundamental to understanding viral persistence and pathobiology. The persistence of HCV, an RNA virus, is especially problematic and HCV stability, maintained despite rapid genomic mutation, is highly paradoxical.

这些病毒传播的感染宿主是大量密切相关的人群，但基因型多变，分子学上称为“相似

种”。 还不清楚，这种极端的基因和抗原多样性，是靠什么机制来维持稳定的；但这是

理解病毒持续存在和病变的基础。HCV( 一种RNA病毒)的持续存在是非常有疑问的；

HCV的稳定性，持续性（而不管在基因快速突变）看上去是很荒谬的。

This paper presents the hypothesis, and evidence, that viruses capable of persistent infection auto regulate replication and the likely mechanism mediating auto regulation--Replicative Homeostasis--is described.

该论文提出的假说和证据——病毒有能力在持续感染期间自动调整复制。可能作为动态

调整的机制是——复制的（群体）自我动态平衡——这在前面介绍过。

Replicative homeostasis causes formation of stable, but highly reactive, equilibria that drive quasispecies expansion and generates escape mutation. Replicative homeostasis explains both viral kinetics and the enigma of RNA quasispecies stability and provides a rational, mechanistic basis for all observed viral behaviours and host responses.

复制的（群体）动态平衡，导致了稳定，但高度灵活，均衡的构成；这驱动了“准物种”

的扩张和产生逃避性变异。“复制的（群体）动态平衡”解释了病毒动力学和“RNA准

物种”稳定性之谜，提出了一个合理的（所有观察到的）病毒行为和宿主反应的基本

机制

More importantly, this paradigm has specific therapeutic implication and defines, precisely, new approaches to antiviral therapy. Replicative homeostasis may also modulate cellular gene expression.

更重要的是，该范例有一个详尽的关于治疗的提示和说明，确切地说，更接近了病毒的

治疗。复制的（群体）动态平衡还可以调整细胞的基因表达。

Note: This article uses highly technical language that many readers will find difficult to follow at times. Although the language is challenging for non scientists, it is worth the effort to read through the entire article, which offers compelling insights into the possible mechanisms of how HIV, HCV and HBV, among other viruses, persist.

注意：该文章使用了非常技术性的语言，很多读者会发现有时很难读懂。虽然这样的语言对非科学家来说是个挑战，但努力读一下整个文章是非常值得的，该文章针对HIV/HCV/HBV如何持续存在，提出了有说服力的见解。

Link to complete text online

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reference R Sallie. Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation. Virology Journal 2(1):10. February 11, 2005

特深沉

病毒是如何躲避免疫系统而存在的(2005.4.26)

复制的（群体）动态平衡：一种新的假说，解释类似HIV,HBV,HBC等病毒，如何持续

存在和躲避免疫控制。

本文提出了一个新的假说，关于类似HIV,HCV,HBV等病毒的持续存在，以及他们怎样

躲避免疫系统的控制。在过去的40天里，这是《病毒学杂志》发表的文章中被下载最

多的文章。（《病毒学杂志》是由BioMed Central发行的可公开获得的期刊。这意味着每

个人都可以免费阅读在这里发表的那些文章。）

该文章解释了为什么RNA病毒，像HCV, HIV, 西尼罗病毒/黄热病/SARS/埃博拉病毒，

等等，如何持续存在，论证了一种基因型/物种机制；因应免疫和其他压力而产生逃避

突变。这解释了为什么干扰素会在很多HCV病例中失败，还解释了抗体增进疾病的机

制。该文还提示针对西尼罗病毒/HCV/HIV/HBV等疾病新颖的治疗方法是可能的，并描

述了可能采用的形式。

HCV，HBC, HIV，和其他通过RNA复制为中介的病毒，在全世界造成了巨大的疾病

负担和过早死亡

这些病毒传播的感染宿主是大量密切相关的人群，但基因型多变，分子学上称为“相似

种”。 还不清楚，这种极端的基因和抗原多样性，是靠什么机制来维持稳定的；但这是

理解病毒持续存在和病变的基础。HCV( 一种RNA病毒)的持续存在是非常有疑问的；

HCV的稳定性，持续性（而不管在基因快速突变）看上去是很荒谬的。

该论文提出的假说和证据——病毒有能力在持续感染期间自动调整复制。可能作为动态

调整的机制是——复制的（群体）自我动态平衡——这在前面介绍过。

复制的（群体）动态平衡，导致了稳定，但高度灵活，均衡的构成；这驱动了“准物种”

的扩张和产生逃避性变异。“复制的（群体）动态平衡”解释了病毒动力学和“RNA准

物种”稳定性之谜，提出了一个合理的（所有观察到的）病毒行为和宿主反应的基本

机制

更重要的是，该范例有一个详尽的关于治疗的提示和说明，确切地说，更接近了病毒的

治疗。复制的（群体）动态平衡还可以调整细胞的基因表达。

注意：该文章使用了非常技术性的语言，很多读者会发现有时很难读懂。虽然这样的语

言对非科学家来说是个挑战，但努力读一下整个文章是非常值得的，该文章针对HIV/

HCV/HBV如何持续存在，提出了有说服力的见解。

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