Replicative homeostasis: a mechanism of viral persistence.

Abstract:

:Acute viral infection is characterised by high-level replication before prompt decline of viraemia and, commonly, viral clearance. This kinetic pattern is generally held to be due to immune control. However, infection with some viruses, notably hepatitis C (HCV), hepatitis B (HBV) and the human immunodeficiency virus (HIV), often results in chronic stable low-level spontaneously fluctuating viraemia, kinetics that are difficult to rationalize on this basis. The persistence of HCV, an RNA virus, is especially problematic and its stability, occurring despite rapid, genomic mutation is highly paradoxical. This paper outlines the hypothesis, and evidence, that viruses autoregulate replication and mutation and describes a mechanism--replicative homeostasis--explaining viral stability. Replicative homeostasis results in stable, but reactive, replicative equilibria that drive quasispecies expansion and immune escape and explain all observed viral behaviours and host responses. This paradigm implies new approaches to antiviral therapy and is broadly relevant to modulation of gene expression.

journal_name

Med Hypotheses

journal_title

Medical hypotheses

authors

Sallie R

doi

10.1016/j.mehy.2004.02.050

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

515-23

issue

3

eissn

0306-9877

issn

1532-2777

pii

S0306987704001689

journal_volume

63

pub_type

杂志文章
  • Astrocyte domains and the three-dimensional and seamless expression of consciousness and explicit memories.

    abstract:UNLABELLED:The expression of consciousness and the site of memory storage within the brain are unknown despite over a century of intense empirical scrutiny. Recent anatomical studies show that human protoplasmic astrocytes form innumerable uniform polyhedral tessellating domains that are arranged three-dimensionally. T...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2013.09.021

    authors: Robertson JM

    更新日期:2013-12-01 00:00:00

  • Energy metabolism in cancer cells: how to explain the Warburg and Crabtree effects?

    abstract::Cancer cells have a greater need for energy and a ready supply of the building blocks necessary for the synthesis of macromolecules (nucleotides, protein, lipids) in order to duplicate genome and biomass. The hypothesis can be postulated that those precursors for synthetic processes, which can only be furnished by gly...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2012.06.002

    authors: Dell' Antone P

    更新日期:2012-09-01 00:00:00

  • Efficacy and safety of Huachansu combined with chemotherapy in advanced gastric cancer: a meta-analysis.

    abstract:BACKGROUND:Huachansu, a Chinese medicine that comes from dried toad venom from the skin glands of Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, has been used in treatment of cancers. We conducted a meta-analysis to evaluate the efficacy and safety of Huachansu combined with chemotherapy for advanced gas...

    journal_title:Medical hypotheses

    pub_type: 杂志文章,meta分析

    doi:10.1016/j.mehy.2013.04.038

    authors: Xie X,Huang X,Li J,Lv X,Huang J,Tang S,Sun Y

    更新日期:2013-08-01 00:00:00

  • Atrial fibrillation: In the light of new hypothesis.

    abstract:BACKGROUND:Atrial fibrillation (AF) is the most common cardiac arrhythmia. Many studies have investigated the cause for the development of AF, however, the question remains unanswered. METHODS:A comparison of hydrodynamics between AF and sinus rhythm was performed. RESULTS:I proposed the hypothesis that atrial fibril...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2015.11.028

    authors: Tilman V

    更新日期:2016-01-01 00:00:00

  • Repression of the enzyme lactate dehydrogenase and the spontaneous remission or regression of cancer.

    abstract::Lactic acid produced by the malignant tumor is what keeps the malignancy going. Suppression or the removal of lactic acid is the prerequisite for any cancer treatment. ...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1054/mehy.2000.1227

    authors: Niakan B

    更新日期:2001-05-01 00:00:00

  • An extended hypothetical theory of the dose-response relations in pharmacology.

    abstract::The authors present an extended version of Clark's and Ariëns's classical theory that enables the interpretation and quantitative characterization of dose-response curves which are not in accordance with classical theory. Being supported by the chemical receptor theory, the new model expands its applicability to two o...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/0306-9877(85)90063-5

    authors: Várkonyi P,Gabányi Z,Körmöczy P

    更新日期:1985-04-01 00:00:00

  • Clues to prolific productivity among prominent scientists.

    abstract::In a survey based on the biographical sketches, obituary notes and eulogies of notable scientists, eight were identified as belonging to an elite group, having authored more than 1000 research publications, which include books, monographs and patents. They were, in chronological order, Thomas Alva Edison, Paul Karrer,...

    journal_title:Medical hypotheses

    pub_type: 历史文章,杂志文章

    doi:10.1016/0306-9877(92)90179-g

    authors: Kantha SS

    更新日期:1992-10-01 00:00:00

  • Genotrim, a DNA-customized nutrigenomic product, targets genetic factors of obesity: hypothesizing a dopamine-glucose correlation demonstrating reward deficiency syndrome (RDS).

    abstract::Obesity is the second largest cause of preventable death in the United States. Historically, obesity was considered a behavioral problem that could be simply addressed with behavioral modifications in diet and exercise. As scientific advancements have demonstrated in other neurological healthcare conditions such as al...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2006.08.041

    authors: Blum K,Chen TJ,Meshkin B,Downs BW,Gordon CA,Blum S,Mangucci JF,Braverman ER,Arcuri V,Deutsch R,Pons MM

    更新日期:2007-01-01 00:00:00

  • Treatment-induced stress syndromes.

    abstract::Placebo controlled trials in disease states as currently constituted are designed to show a drug "works" when in fact it may not. Efficacy of this type may be constructed in trials that demonstrate some marginal superiority of a drug over placebo in disease states that do not take into account any potentialities of th...

    journal_title:Medical hypotheses

    pub_type: 社论,历史文章,评审

    doi:10.1016/j.mehy.2010.01.038

    authors: Healy D

    更新日期:2010-05-01 00:00:00

  • A possible haemodynamic mechanism for amyotrophic lateral sclerosis.

    abstract::The hypothesis proposed in this article is that a haemodynamic mechanism may cause amyotrophic lateral sclerosis (ALS). The hypothesis is synthesized from three separate streams of medical research: (1) multiple sclerosis (MS) research; (2) ALS research; (3) atherosclerosis research. Each research stream was reviewed ...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2010.03.017

    authors: Arhart RW

    更新日期:2010-10-01 00:00:00

  • Can free radicals induce coronary vasospasm and acute myocardial infarction?

    abstract::Spontaneous acute occlusion of the coronary artery produces regional myocardial ischemia and infarction. This coronary occlusion could be due to rapid progression of atherosclerosis or vasospasm. The factors that can precipitate an acute attack of myocardial infarction or coronary spasm are not known. It is proposed t...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/0306-9877(92)90147-5

    authors: Das UN

    更新日期:1992-09-01 00:00:00

  • A possible involvement of crosstalk between advanced glycation end products (AGEs) and asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor in accelerated atherosclerosis in diabetes.

    abstract::Endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) is an early step in the course of atherosclerotic cardiovascular disease (CVD). NO is synthesized from L-arginine via the action of NO synthase (NOS), which is known to be blocked by endogenous L-arginine analogues such as asymmetric dimethyla...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2007.01.053

    authors: Yamagishi S,Ueda S,Okuda S

    更新日期:2007-01-01 00:00:00

  • Moderate osteoporosis itself is beneficial for bones.

    abstract::There have been increasing numbers of reports that anti-osteoporosis drugs cause osteonecrosis. A typical example is medication-related osteonecrosis of the jaws (MRONJ) which can cause massive necrosis and defects of the jaws. Thus, the dosage and effects of anti-osteoporosis drugs should be re-examined. Our hypothes...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2019.109427

    authors: Xiong Z,Wu J,Liu Z,Jing W

    更新日期:2020-01-01 00:00:00

  • Cell hydration as the primary factor in carcinogenesis: A unifying concept.

    abstract::The paper discusses the unifying concept that cell hydration is the primary factor in the mechanism of carcinogenesis. The concept includes the following hypotheses: (1) Increased cell hydration causes cancer not only by promoting cell division and oncogene expression, but also by inactivating genes inducing cell diff...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2005.09.022

    authors: McIntyre GI

    更新日期:2006-01-01 00:00:00

  • Pathogenic effects of the human chemical biofield.

    abstract::Organisms release their antigens into the environment. Some antigens are volatile and may pass into the blood of other organisms during respiration. Fetal antigens enter the mother's bloodstream through the placenta. Foreign antigens in the blood can cause various chemical changes and may initiate an immune reaction. ...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/0306-9877(95)90211-2

    authors: Rumyantsev SN,Grzeszczuk J

    更新日期:1995-07-01 00:00:00

  • Reposition of montelukast either alone or in combination with levocetirizine against SARS-CoV-2.

    abstract::It has been hypothesised that antiallergic medications (AAMs) like montelukast and levocetirizine both the two bitter chloro compounds could be repurposed either alone or combinedly as an antiviral against SARS-CoV-2, like chloroquine/hydroxychloroquine (CQ/HCQ), another two bitter chloro compounds. Both AAMs and CQ/H...

    journal_title:Medical hypotheses

    pub_type: 信件

    doi:10.1016/j.mehy.2020.110046

    authors: Bhattacharyya D

    更新日期:2020-11-01 00:00:00

  • Addictive potential: A=E/T(max)xt(1/2).

    abstract::This hypothesis named Salerian Addictive Potential (SAP) suggests that the addictive potency of any substance may be calculated with an algebraic equation of A=E/T(max)xt(1/2), where A is the addictive potency, E represents the euphoric potency, T(max) is the time to reach peak plasma concentration, and t(1/2) is the ...

    journal_title:Medical hypotheses

    pub_type: 杂志文章,评审

    doi:10.1016/j.mehy.2010.01.008

    authors: Salerian AJ

    更新日期:2010-06-01 00:00:00

  • Speculations on the initiation of chromosome replication in Escherichia coli: the dualism hypothesis.

    abstract::The exact nature of the mechanism that triggers initiation of chromosome replication in the best understood of all organisms, Escherichia coli, remains mysterious. Here, I suggest that this mechanism evolved in response to the problems that arise if chromosome replication does not occur. E. coli is now known to be hig...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2011.02.002

    authors: Norris V

    更新日期:2011-05-01 00:00:00

  • Tracing the origins of "fetal origins" of adult diseases: programming by oxidative stress?

    abstract::Too small size at birth (due to poor fetal growth and/or preterm delivery) has been associated with substantially elevated risks of the metabolic syndrome (dislipidemia, insulin resistance, hypertension), type 2 diabetes and cardiovascular disease in adulthood. The mechanisms of such "fetal origins" or "programming" o...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2005.08.020

    authors: Luo ZC,Fraser WD,Julien P,Deal CL,Audibert F,Smith GN,Xiong X,Walker M

    更新日期:2006-01-01 00:00:00

  • Does hypoxemia prevent brain damage in birth asphyxia?

    abstract::The clinical syndrome of hypoxic ischemic encephalopathy (HIE) which occurs in association with birth asphyxia, is thought to represent a reperfusion injury consequent upon the generation of cytotoxic oxygen derived free radicals. It has recently been suggested that resuscitation of asphyxiated infants with unrestrict...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/0306-9877(93)90080-a

    authors: Ballot DE,Rothberg AD,Davies VA,Smith J,Kirsten G

    更新日期:1993-10-01 00:00:00

  • Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer.

    abstract::Cocaine is one of the principal drugs of abuse. Although impressive advances have been made, unanswered questions remain concerning mechanism of toxicity and addiction. Discussion of action mode usually centers on receptor binding and enzyme inhibition, with limited attention to events at the molecular level. This rev...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2004.06.028

    authors: Kovacic P

    更新日期:2005-01-01 00:00:00

  • The role of dietary ergothioneine in the development of diabetes mellitus.

    abstract::Ergothioneine is believed not to be synthesized by man but it accumulates to high concentrations in some mammalian cells as a result of dietary intake. Ergothioneine is known to chelate divalent metal ions with high affinity. Other substances which are potent chelators of divalent metal ions such as diphenylthiocarbaz...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/0306-9877(82)90137-2

    authors: Epand RM

    更新日期:1982-08-01 00:00:00

  • The hyponatramia of multiple myeloma is true and not pseudohyponatramia.

    abstract::The hyponatremia found in multiple myeloma and which is associated with a reduced anion gap (ag) is considered to be pseudohyponatremia due to the displacement of water by the high globulin content in the blood. Serum proteins participate in acid-base balance. Stewart and other authors in their approach to acid-base i...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2006.02.051

    authors: Sachs J,Fredman B

    更新日期:2006-01-01 00:00:00

  • Melanoma. Shall we move away from the sun and focus more on embryogenesis, body weight and longevity?

    abstract::There are many observations regarding the behaviour of melanoma which points away from sunshine as the main cause of this tumour. Incidence data shows that the increase is mostly seen for thin melanomas which cannot be attributed to sun exposure but increasing screening over the last 20 years. Melanoma behaves in a si...

    journal_title:Medical hypotheses

    pub_type: 杂志文章,评审

    doi:10.1016/j.mehy.2013.05.031

    authors: Bataille V

    更新日期:2013-11-01 00:00:00

  • Unifying concepts in mechanism of amblyopia.

    abstract::Most of the evidence of formation of amblyopia is derived traditionally from electrophysiological studies. Recently, there have been many discoveries from genetics, histopathology, biochemistry, immunology and interventional studies. On the basis of evidence gathered in the last five years, the various types of amblyo...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/s0306-9877(97)90275-9

    authors: Tong LM

    更新日期:1997-02-01 00:00:00

  • Does tumor necrosis factor play a role in the pathogenesis of fulminant hepatitis?

    abstract::Fulminant hepatitis is associated with an 80% mortality rate. Surviving patients do not develop chronic liver disease. Failure to produce adequate amounts of interferon and to achieve an antiviral state seem to be the basic defects in this condition. Tumor necrosis factor (TNF) has been shown to be induced by viruses....

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/0306-9877(88)90140-5

    authors: Aderka D,Levo Y

    更新日期:1988-11-01 00:00:00

  • Pharmacological manipulation of ataxia-telangiectasia kinase activity as a treatment for Parkinson's disease.

    abstract::Parkinson's disease (PD) is a major cause of morbidity and mortality among older individuals. Although the causes of Parkinson's disease are multifactorial, considerable evidence indicates that elevated labile iron in the substantia nigra pars compacta plays an important role in producing oxyradicals which subsequentl...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2004.08.029

    authors: Edwin Shackelford R,Manuszak RP,Heard SC,Link CJ,Wang S

    更新日期:2005-01-01 00:00:00

  • Positional nystagmus in middle ear cholesteatoma with labyrinthine fistula.

    abstract::Chronic otitis media with cholesteatoma can cause erosion of the dense labyrinthine bone overlying the inner ear organs, and this labyrinthine fistula allows pressure or mass-induced motion of the underlying perilymphatic and endolymphatic compartment, evoking vestibular symptoms. While the mechanism of a positive fis...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2020.110223

    authors: Jeong H,Lee DH,Shin JE,Kim CH

    更新日期:2020-11-01 00:00:00

  • Elimination of major side effects due to ROS of therapeuticals through biotransformation control of the 57 cytochromes P450 isoenzymes.

    abstract::Drug biotransformations are controlled in the body by tissue-differentiated choice of a selection of the induced and constitutive 57 isoforms of the human cytochromes P450 (CYP). CYP are the mixed function oxidase enzyme family (EC 1.14.14.1: mono-oxygenases that contain iron-dependent protohaematin IX). Many of the m...

    journal_title:Medical hypotheses

    pub_type: 杂志文章

    doi:10.1016/j.mehy.2004.10.010

    authors: Wiseman A

    更新日期:2005-01-01 00:00:00

  • The changing scene in Hashimoto's disease: a review.

    abstract::The review briefly describes the evolution of hypotheses about cronic thyroiditis, the escape of colloid hypothesis, basement membrane destruction, the auto-immune theory and the role of disregulatory genes. ...

    journal_title:Medical hypotheses

    pub_type: 杂志文章,评审

    doi:10.1016/j.mehy.2011.05.035

    authors: Stuart A

    更新日期:2011-09-01 00:00:00