This interactome records Borna virus interactions with diverse host proteins and genes
Kegg Pathway analysis of the host arm of the interactome is provided here
Kegg Pathway analysis of the host arm of the interactome is provided here
Showing posts with label Borna virus. Show all posts
Showing posts with label Borna virus. Show all posts
Borna Disease Virus Phosphoprotein Modulates Epigenetic Signaling in Neurons To Control Viral Replication
Understanding the modalities of interaction of neurotropic viruses with their target cells represents a major challenge that may improve our knowledge of many human neurological disorders for which viral origin is suspected. Borna disease virus (BDV) represents an ideal model to analyze the molecular mechanisms of viral persistence in neurons and its consequences for neuronal homeostasis. It is now established that BDV ensures its long-term maintenance in infected cells through a stable interaction of viral components with the host cell chromatin, in particular, with core histones. This has led to our hypothesis that such an interaction may trigger epigenetic changes in the host cell. Here, we focused on histone acetylation, which plays key roles in epigenetic regulation of gene expression, notably for neurons. We performed a comparative analysis of histone acetylation patterns of neurons infected or not infected by BDV, which revealed that infection decreases histone acetylation on selected lysine residues. We showed that the BDV phosphoprotein (P) is responsible for these perturbations, even when it is expressed alone independently of the viral context, and that this action depends on its phosphorylation by protein kinase C. We also demonstrated that BDV P inhibits cellular histone acetyltransferase activities. Finally, by pharmacologically manipulating cellular acetylation levels, we observed that inhibiting cellular acetyl transferases reduces viral replication in cell culture. Our findings reveal that manipulation of cellular epigenetics by BDV could be a means to modulate viral replication and thus illustrate a fascinating example of virus-host cell interaction.
IMPORTANCE Persistent DNA viruses often subvert the mechanisms that regulate cellular chromatin dynamics, thereby benefitting from the resulting epigenetic changes to create a favorable milieu for their latent and persistent states. Here, we reasoned that Borna disease virus (BDV), the only RNA virus known to durably persist in the nucleus of infected cells, notably neurons, might employ a similar mechanism. In this study, we uncovered a novel modality of virus-cell interaction in which BDV phosphoprotein inhibits cellular histone acetylation by interfering with histone acetyltransferase activities. Manipulation of cellular histone acetylation is accompanied by a modulation of viral replication, revealing a perfect adaptation of this “ancient” virus to its host that may favor neuronal persistence and limit cellular damage.
Borna Disease Virus Phosphoprotein Impairs the Developmental Program Controlling Neurogenesis and Reduces Human GABAergic Neurogenesis.
It is well established that persistent viral infection may impair
cellular function of specialized cells without overt damage. This
concept, when applied to neurotropic viruses, may help to understand
certain neurologic and neuropsychiatric diseases. Borna disease virus
(BDV) is an excellent example of a persistent virus that targets the
brain, impairs neural functions without cell lysis, and ultimately
results in neurobehavioral disturbances. Recently, we have shown that
BDV infects human neural progenitor cells (hNPCs) and impairs
neurogenesis, revealing a new mechanism by which BDV may interfere with
brain function. Here, we sought to identify the viral proteins and
molecular pathways that are involved. Using lentiviral vectors for
expression of the bdv-p and bdv-x viral genes, we demonstrate that the
phosphoprotein P, but not the X protein, diminishes human neurogenesis
and, more particularly, GABAergic neurogenesis. We further reveal a
decrease in pro-neuronal factors known to be involved in neuronal
differentiation (ApoE, Noggin, TH and Scg10/Stathmin2), demonstrating
that cellular dysfunction is associated with impairment of specific
components of the molecular program that controls neurogenesis. Our
findings thus provide the first evidence that a viral protein impairs
GABAergic human neurogenesis, a process that is dysregulated in several
neuropsychiatric disorders. They improve our understanding of the
mechanisms by which a persistent virus may interfere with brain
development and function in the adult.
cellular function of specialized cells without overt damage. This
concept, when applied to neurotropic viruses, may help to understand
certain neurologic and neuropsychiatric diseases. Borna disease virus
(BDV) is an excellent example of a persistent virus that targets the
brain, impairs neural functions without cell lysis, and ultimately
results in neurobehavioral disturbances. Recently, we have shown that
BDV infects human neural progenitor cells (hNPCs) and impairs
neurogenesis, revealing a new mechanism by which BDV may interfere with
brain function. Here, we sought to identify the viral proteins and
molecular pathways that are involved. Using lentiviral vectors for
expression of the bdv-p and bdv-x viral genes, we demonstrate that the
phosphoprotein P, but not the X protein, diminishes human neurogenesis
and, more particularly, GABAergic neurogenesis. We further reveal a
decrease in pro-neuronal factors known to be involved in neuronal
differentiation (ApoE, Noggin, TH and Scg10/Stathmin2), demonstrating
that cellular dysfunction is associated with impairment of specific
components of the molecular program that controls neurogenesis. Our
findings thus provide the first evidence that a viral protein impairs
GABAergic human neurogenesis, a process that is dysregulated in several
neuropsychiatric disorders. They improve our understanding of the
mechanisms by which a persistent virus may interfere with brain
development and function in the adult.
Borna disease virus phosphoprotein modulates epigenetic signaling in neurons to control viral replication.
Understanding the modalities
of interaction of neurotropic viruses with their target cells represents
a major challenge that may improve our knowledge of many human
neurological disorders for which viral origin is suspected. Borna
disease virus (BDV) represents an ideal model to analyze the molecular
mechanisms of viral persistence in neurons and its consequences for
neuronal homeostasis. It is now established that BDV ensures its
long-term maintenance in infected cells through a stable interaction of
viral components with the host cell chromatin, in particular with core
histones. This has led to our hypothesis that such an interaction may
trigger epigenetic changes in the host cell. Here, we focused on histone
acetylation, which play key roles in epigenetic regulation of gene
expression, notably for neurons. We performed a comparative analysis of
histone acetylation patterns of neurons infected or not by BDV, which
revealed that infection decreases histone acetylation on selected lysine
residues. We showed that the BDV phosphoprotein (P) is responsible for
these perturbations, even when expressed alone independently of the
viral context, and that this action depends on its phosphorylation by
protein kinase C. We also demonstrated that BDV P inhibits cellular
histone acetyl transferase activities. Finally, by pharmacologically
manipulating cellular acetylation levels, we observed that inhibiting
cellular acetyl transferases reduces viral replication in cell culture.
Our findings reveal that manipulation of cellular epigenetics by BDV
could be a mean to modulate viral replication and thus illustrate a
fascinating example of virus/host cell interaction.
DNA viruses often subvert the mechanisms that regulate cellular
chromatin dynamics, thereby benefitting from the resulting epigenetic
changes to create a favorable milieu for their latent/persistent states.
Here, we reasoned that Borna Disease Virus (BDV), the only RNA virus
known to durably persist in the nucleus of infected cells, notably
neurons, might employ a similar mechanism. In this study, we uncover a
novel modality of virus/cell interaction in which BDV phosphoprotein
inhibits cellular histone acetylation by interfering with histone acetyl
transferase activities. Manipulation of cellular histone acetylation is
accompanied by a modulation of viral replication, revealing the perfect
adaptation of this "ancient" virus to its host that may favor neuronal
persistence and limit cellular damage.
of interaction of neurotropic viruses with their target cells represents
a major challenge that may improve our knowledge of many human
neurological disorders for which viral origin is suspected. Borna
disease virus (BDV) represents an ideal model to analyze the molecular
mechanisms of viral persistence in neurons and its consequences for
neuronal homeostasis. It is now established that BDV ensures its
long-term maintenance in infected cells through a stable interaction of
viral components with the host cell chromatin, in particular with core
histones. This has led to our hypothesis that such an interaction may
trigger epigenetic changes in the host cell. Here, we focused on histone
acetylation, which play key roles in epigenetic regulation of gene
expression, notably for neurons. We performed a comparative analysis of
histone acetylation patterns of neurons infected or not by BDV, which
revealed that infection decreases histone acetylation on selected lysine
residues. We showed that the BDV phosphoprotein (P) is responsible for
these perturbations, even when expressed alone independently of the
viral context, and that this action depends on its phosphorylation by
protein kinase C. We also demonstrated that BDV P inhibits cellular
histone acetyl transferase activities. Finally, by pharmacologically
manipulating cellular acetylation levels, we observed that inhibiting
cellular acetyl transferases reduces viral replication in cell culture.
Our findings reveal that manipulation of cellular epigenetics by BDV
could be a mean to modulate viral replication and thus illustrate a
fascinating example of virus/host cell interaction.
IMPORTANCE:
PersistentDNA viruses often subvert the mechanisms that regulate cellular
chromatin dynamics, thereby benefitting from the resulting epigenetic
changes to create a favorable milieu for their latent/persistent states.
Here, we reasoned that Borna Disease Virus (BDV), the only RNA virus
known to durably persist in the nucleus of infected cells, notably
neurons, might employ a similar mechanism. In this study, we uncover a
novel modality of virus/cell interaction in which BDV phosphoprotein
inhibits cellular histone acetylation by interfering with histone acetyl
transferase activities. Manipulation of cellular histone acetylation is
accompanied by a modulation of viral replication, revealing the perfect
adaptation of this "ancient" virus to its host that may favor neuronal
persistence and limit cellular damage.
Borna disease virus (BDV) infection in psychiatric patients and healthy controls in Iran.
BACKGROUND:
Borna disease virus (BDV) is an evolutionary old RNA virus, which infects brain and blood cells ofhumans, their primate ancestors, and other mammals. Human infection has been correlated to mood disorders and schizophrenia, but the impact of BDV on mental-health still remains controversial due to poor methodological and cross-national comparability.
METHOD:
Thisfirst report from the Middle East aimed to determine BDV infection
prevalence in Iranian acute psychiatric disorder patients and healthy
controls through circulating immune complexes (CIC), antibodies (Ab) and
antigen (pAg) in blood plasma using a standardized triple enzyme immune
assay (EIA). Samples of 314 subjects (114 psychiatric cases, 69 blood
donors, and 131 healthy controls) were assayed and data analyzed
quantitatively and qualitatively.
RESULTS:
CICs revealed a BDV prevalence of one third (29.5%) in healthy Iranian controls (27.5%controls; 33.3% blood donors). In psychiatric patients CIC prevalence
was higher than in controls (40.4%) and significantly correlating with
bipolar patients exhibiting overt clinical symptoms (p = 0.005, OR =
1.65). CIC values were significantly elevated in bipolar (p = 0.001) and
major depressive disorder (p = 0.029) patients as compared to controls,
and in females compared to males (p = 0.031).
CONCLUSION:
This study supports a similarly high prevalence of subclinical human BDVinfections in Iran as reported for central Europe, and provides again an
indication for the correlation of BDV infection and mood disorders.
Further studies should address the morbidity risk for healthy carriers
and those with elevated CIC levels, along with gender disparities.
Meta-Analysis of Infectious Agents and Depression.
Depression is a debilitating psychiatric disorder and a growing global
public health issue. However, the relationships between microbial
infections and depression remains uncertain. A computerized literature
search of Medline, ISI Web of Knowledge, PsycINFO, and the Cochrane
Library was conducted up to May 2013, and 6362 studies were initially
identified for screening. Case-control studies detected biomarker of
microorganism were included. Based on inclusion and exclusion criteria,
28 studies were finally included to compare the detection of 16
infectious agents in unipolar depressed patients and healthy controls
with a positive incident being defined as a positive biochemical marker
of microbial infection. A customized form was used for data extraction.
Pooled analysis revealed that the majority of the 16 infectious agents
were not significantly associated with depression. However, there were
statistically significant associations between depression and infection
with Borna disease virus, herpes simplex virus-1, varicella zoster
virus, Epstein-Barr virus, and Chlamydophila trachomatis.
public health issue. However, the relationships between microbial
infections and depression remains uncertain. A computerized literature
search of Medline, ISI Web of Knowledge, PsycINFO, and the Cochrane
Library was conducted up to May 2013, and 6362 studies were initially
identified for screening. Case-control studies detected biomarker of
microorganism were included. Based on inclusion and exclusion criteria,
28 studies were finally included to compare the detection of 16
infectious agents in unipolar depressed patients and healthy controls
with a positive incident being defined as a positive biochemical marker
of microbial infection. A customized form was used for data extraction.
Pooled analysis revealed that the majority of the 16 infectious agents
were not significantly associated with depression. However, there were
statistically significant associations between depression and infection
with Borna disease virus, herpes simplex virus-1, varicella zoster
virus, Epstein-Barr virus, and Chlamydophila trachomatis.
Evidence for Borna disease virus infection in neuropsychiatric patients in three western China provinces.
Borna disease virus (BDV) is a non-cytolytic, neurotropic RNA virus that can infect a wide variety of vertebrate species from birds and primates to humans. Several studies have been carried out to investigate whether BDV is associated with neuropsychiatric diseases. However, this association is still inconclusive. Two panels of subjects consisting of 1,679 various neuropsychiatric patients and healthy people from three western China provinces were enrolled in this study. BDV p24 or p40 RNA in peripheral blood mononuclear cells (PBMCs) were detected in the first panel of 1,481 subjects using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and cerebrospinal fluid (CSF) samples from the BDV RNA-positive individuals were subjected to BDV p24 antibodies testing by enzyme-linked immunosorbent assay (ELISA). BDV p24 or p40 RNA in PBMCs and p24 antibodies in plasma were detected in the second panel of 198 subjects by RT-qPCR and Western blot. A higher prevalence for BDV RNA was demonstrated in patients with viral encephalitis (6.70 %), Guillain-Barré syndrome (6.70 %), schizophrenia (9.90 %) and chronic fatigue syndrome (CFS) (12.70 %) compared to healthy controls in the first panel. CSF p24 antibodies were demonstrated in three viral encephalitis patients, two schizophrenia patients and two major depressive disorder (MDD) patients. The prevalences of p24 antibodies in plasma from patients with viral encephalitis (13.24 %), multiple sclerosis (25.00 %) and Parkinson's disease (22.73 %) were significantly higher than healthy controls. This study demonstrates that BDV infection also exists in humans from three western China provinces, and suggests the involvement of the contribution of BDV in the aetiology of Chinese patients with some neuropsychiatric disorders, including viral encephalitis, schizophrenia, CFS, multiple sclerosis and Parkinson's disease.
Prospects for cannabinoid therapies in viral encephalitis.
Cannabinoids are promising therapies to support neurogenesis and decelerate disease progression in neuroinflammatory and degenerative disorders. Whether neuroprotective effects of cannabinoids are sustainable during persistent viral infection of the CNS is not known. Using a rodent model of chronic viral encephalitis based on Borna Disease (BD) virus, in which 1 week treatment with the general cannabinoid WIN 55,212-2 has been shown to be neuroprotective (Solbrig et al., 2010), we examine longer term (2 week treatment) effects of a general (CB1 and CB2) cannabinoid receptor agonist WIN55,212-2 (1mg/kg ip twice per day) or a specific (CB2) cannabinoid receptor agonist HU-308 (5mg/kg ip once daily) on histopathology, measures of frontostriatal neurogenesis and gliogenesis, and viral load. We find WIN and HU-308 differ in their ability to protect new BrdU+cells. The selective CB2 agonist HU increases BrdU+ cells in prefrontal cortex (PFC), significantly increases BrdU+ cells in striatum, differentially regulates polydendrocytes vs microglia/macrophages, and reduces immune activation at a time WIN-treated rats appear tolerant to the anti-inflammatory effect of their cannabinoid treatment. WIN and HU had little direct viral effect in PFC and striatum, yet reduced viral signal in hippocampus. Thus, HU-308 action on CB2 receptors, receptors known to be renewed during microglia proliferation and action, is a nontolerizing mechanism of controlling CNS inflammation during viral encephalitis by reducing microglia activation, as well as partially limiting viral infection, and uses a nonpsychotropic cannabinoid agonist.
Human but Not Laboratory Borna Disease Virus Inhibits Proliferation and Induces Apoptosis in Human Oligodendrocytes In Vitro.
Borna disease virus (BDV) is a neurotropic virus that produces neuropsychiatric dysfunction in a wide range of warm-blooded species. Several studies have associated BDV with human psychiatric illness, but the findings remain controversial. Although oligodendrocytes are a major glial component of brain white matter and play a pivotal role in neuronal cell function, BDV's effects on human oligodendrocytes have not been clarified. Here, the effects of two BDV strains, Hu-H1 (isolated from a bipolar patient) and Strain V (a laboratory strain), on the proliferation and apoptosis of human oligodendrocytes were investigated. Three experimental cell lines were constructed: Hu-H1-infected oligodendroglioma (Hu-H1) cells, Strain V-infected oligodendroglioma (Strain V) cells, and non-infected oligodendroglioma (control) cells. BDV infection was assayed by BDV nucleoprotein (p40) immunofluorescence, cell proliferation was assayed by Cell Counting Kit-8 (CCK8), and cell cycle phases and apoptosis were assayed by flow cytometry. Expressions of the apoptosis-related proteins Bax and Bcl-2 were measured by Western blotting. p40 expression was confirmed in Hu-H1 and Strain V on and after day three post-infection. Strain V cells showed significantly greater cellular proliferation than Hu-H1 cells on and after day three post-infection. In Hu-H1 cells, Bax and Bcl-2 expression were significantly increased and decreased, respectively, on and after day three post-infection. In contrast, in Strain V cells, Bax and Bcl-2 expression were significantly decreased and increased, respectively, on and after day three post-infection. In conclusion, Hu-H1 inhibits cellular proliferation and promotes apoptosis in human oligodendrocytes via Bax upregulation and Bcl-2 downregulation. In contrast, Strain V promotes cellular proliferation and inhibits apoptosis in human oligodendrocytes via Bax downregulation and Bcl-2 upregulation. The effects of the Hu-H1 strain (isolated from a bipolar patient) are opposite from those of Strain V (a laboratory strain), thereby providing a proof of authenticity for both.
Borna disease virus-induced neuronal degeneration dependent on host genetic background and prevented by soluble factors.
Infection of newborn rats with Borne disease virus (BDV) results in selective degeneration of granule cell neurons of the dentate gyrus (DG). To study cellular countermechanisms that might prevent this pathology, we screened for rat strains resistant to this BDV-induced neuronal degeneration. To this end, we infected hippocampal slice cultures of different rat strains with BDV and analyzed for the preservation of the DG. Whereas infected cultures of five rat strains, including Lewis (LEW) rats, exhibited a disrupted DG cytoarchitecture, slices of three other rat strains, including Sprague-Dawley (SD), were unaffected. However, efficiency of viral replication was comparable in susceptible and resistant cultures. Moreover, these rat strain-dependent differences in vulnerability were replicated in vivo in neonatally infected LEW and SD rats. Intriguingly, conditioned media from uninfected cultures of both LEW and SD rats could prevent BDV-induced DG damage in infected LEW hippocampal cultures, whereas infection with BDV suppressed the availability of these factors from LEW but not in SD hippocampal cultures. To gain further insights into the genetic basis for this rat strain-dependent susceptibility, we analyzed DG granule cell survival in BDV-infected cultures of hippocampal neurons derived from the F1 and F2 offspring of the crossing of SD and LEW rats. Genome-wide association analysis revealed one resistance locus on chromosome (chr) 6q16 in SD rats and, surprisingly, a locus on chr3q21-23 that was associated with susceptibility. Thus, BDV-induced neuronal degeneration is dependent on the host genetic background and is prevented by soluble protective factors in the disease-resistant SD rat strain.
PLOS ONE: Borna Disease Virus Infection Perturbs Energy Metabolites and Amino Acids in Cultured Human Oligodendroglia Cells
Borna disease virus is a neurotropic, non-cytolytic virus that has been widely employed in neuroscientific research. Previous studies have revealed that metabolic perturbations are associated with Borna disease viral infection. However, the pathophysiological mechanism underlying its mode of action remains unclear.
METHODOLOGY:
Human oligodendroglia cells infected with the human strain Borna disease virus Hu-H1 and non-infected matched control cells were cultured in vitro. At day 14 post-infection, a proton nuclear magnetic resonance-based metabonomic approach was used to differentiate the metabonomic profiles of 28 independent intracellular samples from Borna disease virus-infected cells (n = 14) and matched control cells (n = 14). Partial least squares discriminant analysis was performed to demonstrate that the whole metabonomic patterns enabled discrimination between the two groups, and further statistical testing was applied to determine which individual metabolites displayed significant differences between the two groups.
FINDINGS:
Metabonomic profiling revealed perturbations in 23 metabolites, 19 of which were deemed individually significant: nine energy metabolites (α-glucose, acetate, choline, creatine, formate, myo-inositol, nicotinamide adenine dinucleotide, pyruvate, succinate) and ten amino acids (aspartate, glutamate, glutamine, glycine, histidine, isoleucine, phenylalanine, threonine, tyrosine, valine). Partial least squares discriminant analysis demonstrated that the whole metabolic patterns enabled statistical discrimination between the two groups.
CONCLUSION:
Borna disease viral infection perturbs the metabonomic profiles of several metabolites in human oligodendroglia cells cultured in vitro. The findings suggest that Borna disease virus manipulates the host cell's metabolic network to support viral replication and proliferation.
TNF-Overexpression in Borna Disease Virus-Infected Mouse Brains Triggers Inflammatory Reaction and Epileptic Seizures.
Proinflammatory state of the brain increases the risk for seizure development. Neonatal Borna disease virus (BDV)-infection of mice with neuronal overexpression of tumor necrosis factor-α (TNF) was used to investigate the complex relationship between enhanced cytokine levels, neurotropic virus infection and reaction pattern of brain cells focusing on its role for seizure induction. Viral antigen and glial markers were visualized by immunohistochemistry. Different levels of TNF in the CNS were provided by the use of heterozygous and homozygous TNF overexpressing mice. Transgenic TNF, total TNF (native and transgenic), TNF-receptor (TNFR1, TNFR2), IL-1 and N-methyl-D-aspartate (NMDA)-receptor subunit 2B (NR2B) mRNA values were measured by real time RT-PCR. BDV-infection of TNF-transgenic mice resulted in non-purulent meningoencephalitis accompanied by epileptic seizures with a higher frequency in homozygous animals. This correlated with lower weight gain, stronger degree and progression of encephalitis and early, strong microglia activation in the TNF-transgenic mice, most obviously in homozygous animals. Activation of astroglia could be more intense and associated with an unusual hypertrophy in the transgenic mice. BDV-antigen distribution and infectivity in the CNS was comparable in TNF-transgenic and wild-type animals. Transgenic TNF mRNA-expression was restricted to forebrain regions as the transgene construct comprised the promoter of NMDA-receptor subunit2B and induced up-regulation of native TNF mRNA. Total TNF mRNA levels did not increase significantly after BDV-infection in the brain of transgenic mice but TNFR1, TNFR2 and IL-1 mRNA values, mainly in the TNF overexpressing brain areas. NR2B mRNA levels were not influenced by transgene expression or BDV-infection. Neuronal TNF-overexpression combined with BDV-infection leads to cytokine up-regulation, CNS inflammation and glial cell activation and confirmed the presensitizing effect of elevated cytokine levels for the development of spontaneous epileptic seizures when exposed to additional infectious noxi.
Infectious agents associated with schizophrenia: A meta-analysis.
Thw results that support the idea that there is a statistically significant association between schizophrenia and infection by Human Herpesvirus 2 (OR=1.34; CI 95%: 1.09-1.70; p=0.05), Borna Disease Virus (OR=2.03; CI 95%: 1.35-3.06; p<0.01), Human Endogenous Retrovirus W (OR=19.31; CI 95%: 6.74-55.29; p<0.001), Chlamydophila pneumoniae (OR=6.34; CI 95%: 2.83-14.19; p<0.001), Chlamydophila psittaci (OR=29.05; CI 95%: 8.91-94.70; p<0.001) and Toxoplasma gondii (OR=2.70; CI 95%: 1.34-4.42; p=0.005). T Schizophrenia
The human genome is composed of viral DNA
Evidence from over 2 million viral/human alignments, shows that the human genome is composed of viral DNA.
This is not just retroviruses (XMRV and HIV-1) but common viruses such as the rhinovirus, Epstein-Barr, influenza, herpes, papillomavirus, coronavirus and many more. This supports the idea, proposed over a century ago, by J.B.S.Haldane and Felix D'Herelle that viruses are responsible for the origin of life, and also the idea that viral inserts are responsible for evolutionary jumps.(the insertion of several viral genes, if passed on through the germ line, effectively creates a new being)
As if that were not interesting enough, here is the important factor , exemplified by Alzheimer's disease Bipolar disorder and schizophrenia. The insertion points of the viruses implicated as risk factors in any particular disease correspond to the locations of the genes implicated in the disease.
The more important the gene in Alzheimer's disease (and others), the more viral proteins it matches (and those of other pathogens).
These viral matches appear to cover the whole human genome, and every human protein is homologous to one virus or another.
In the human genome, these matches are characterised by millions of gapped consecutive and contiguous segments which translate into short contiguous peptide stretches (5-12 amino acids long).The older the viral insertion, the more fragmented the DNA, the shorter the protein matches,but the greater the number of human/viral homologues.
These human protein matches (vatches) are identical to those in the proteins expressed by the viruses implicated in the disease.
Because the viral protein is similar to human receptors, peptide ligands, enzymes, etc it can act as a dummy ligand or a decoy receptor, and also interfere with the interactome of its human counterpart. This is shown quite clearly in the DISC1/viral interactome
Upon infection, antibodies to the virus also risk targeting their human counterparts, which will in effect be knocked down when the antibody binds. The protein equivalent of gene knockouts. If the peptides are highly immunogenic, then cells containing the virus, or its human analogue will be targeted for destruction. This is exemplified by the fact that immunisation with tau in mice provokes the neurofibrillary tangle pathology seen in Alzheimer's disease.Tau is homologous to Herpes simplex and other viral proteins.
All of the diseases on the website pages Alzheimer's disease, Bipolar disorder, Schizophrenia, Chonic fatigue, and more, have an autoimmune component, pathogens are implicated in all, and the genes and pathogens fit together, hand in glove, for all (Bipolar disorder, Alzheimer's and schizophrenia).
Viruses (known and unsuspected culrits) are also homologous to the autoantigens in multiple sclerosis and to the mutant proteins in Huntington's disease and cystic fibrosis (see website)
This suggests that many human diseases work via this common mechanism, and therefore that most are preventable, by vaccination or elimination of the pathogen, and perhaps curable by immunosuppressant therapy.
Examples of how this works are here
A pdf of a prepublication is available at NaturePrecedings.
This is not just retroviruses (XMRV and HIV-1) but common viruses such as the rhinovirus, Epstein-Barr, influenza, herpes, papillomavirus, coronavirus and many more. This supports the idea, proposed over a century ago, by J.B.S.Haldane and Felix D'Herelle that viruses are responsible for the origin of life, and also the idea that viral inserts are responsible for evolutionary jumps.(the insertion of several viral genes, if passed on through the germ line, effectively creates a new being)
As if that were not interesting enough, here is the important factor , exemplified by Alzheimer's disease Bipolar disorder and schizophrenia. The insertion points of the viruses implicated as risk factors in any particular disease correspond to the locations of the genes implicated in the disease.
The more important the gene in Alzheimer's disease (and others), the more viral proteins it matches (and those of other pathogens).
These viral matches appear to cover the whole human genome, and every human protein is homologous to one virus or another.
In the human genome, these matches are characterised by millions of gapped consecutive and contiguous segments which translate into short contiguous peptide stretches (5-12 amino acids long).The older the viral insertion, the more fragmented the DNA, the shorter the protein matches,but the greater the number of human/viral homologues.
These human protein matches (vatches) are identical to those in the proteins expressed by the viruses implicated in the disease.
Because the viral protein is similar to human receptors, peptide ligands, enzymes, etc it can act as a dummy ligand or a decoy receptor, and also interfere with the interactome of its human counterpart. This is shown quite clearly in the DISC1/viral interactome
Upon infection, antibodies to the virus also risk targeting their human counterparts, which will in effect be knocked down when the antibody binds. The protein equivalent of gene knockouts. If the peptides are highly immunogenic, then cells containing the virus, or its human analogue will be targeted for destruction. This is exemplified by the fact that immunisation with tau in mice provokes the neurofibrillary tangle pathology seen in Alzheimer's disease.Tau is homologous to Herpes simplex and other viral proteins.
All of the diseases on the website pages Alzheimer's disease, Bipolar disorder, Schizophrenia, Chonic fatigue, and more, have an autoimmune component, pathogens are implicated in all, and the genes and pathogens fit together, hand in glove, for all (Bipolar disorder, Alzheimer's and schizophrenia).
Viruses (known and unsuspected culrits) are also homologous to the autoantigens in multiple sclerosis and to the mutant proteins in Huntington's disease and cystic fibrosis (see website)
This suggests that many human diseases work via this common mechanism, and therefore that most are preventable, by vaccination or elimination of the pathogen, and perhaps curable by immunosuppressant therapy.
Examples of how this works are here
A pdf of a prepublication is available at NaturePrecedings.
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