Immune response to a flu protein yields new insights into narcolepsy

An international team of researchers has found some of the first solid
evidence that narcolepsy may be a so-called "hit-and-run" autoimmune
disease.

The authors propose a hit-and-run autoimmune mechanism for how both
swine flu and the vaccine Pandemrix might cause narcolepsy. They suggest that in
genetically predisposed people, high levels of the H1N1 protein
stimulate the production of large amounts of antibodies to both the
virus (or vaccine) and the hypocretin receptor. These antibodies may persist in the
blood for months. Either the large numbers of antibodies or inflammation
from an unrelated infection could alter the blood-brain barrier,
allowing the antibodies to enter the brain. There, the antibodies may
latch onto hypocretin receptors, possibly directing the immune system to
destroy or suppress brain cells critical to regulating sleep-wake
cycles.

Viral Infection May Trigger Childhood Diabetes in Utero

The incidence of type 1 childhood diabetes has been increasing rapidly
worldwide. If blood sugar levels aren't well-controlled, juvenile
diabetes can affect nearly every organ of a child's body. And while
long-term complications of the disease develop gradually, they may
become disabling and even life-threatening. The exact cause of juvenile
diabetes has eluded scientists, but a new study from Tel Aviv University suggests a likely trigger before birth.

In a recent paper published in Diabetic Medicine, Prof. Zvi Laron, Professor Emeritus of Pediatric Endocrinology at TAU's Sackler Faculty of Medicine,
Director of the Endocrinology and Diabetes Research Unit at Schneider
Children's Medical Center of Israel, and Head of the WHO Collaborating
Center for the Study of Diabetes in Youth, puts forth evidence that the
autoimmune disease is initiated in utero. According to the
research, conducted in collaboration with an international team of
researchers, women who contract a viral infection during pregnancy
transmit viruses to their genetically susceptible fetuses, sparking the
development of type 1 diabetes.

Antibodies to islet cell autoantigens, rotaviruses and/or enteroviruses in cord blood and healthy mothers in relation to the 2010–2011 winter viral seasons in Israel: a pilot study

Single Amino Acid Repeats Connect Viruses to Neurodegeneration.

We report on a high level of octapeptide matching between HCV, HIV-2,
MPV, MUV, EBV, HHV-6, and CMV, and human brain antigens that, when
altered, have been specifically associated with neuropathologies such as
amyotrophic lateral sclerosis, spinocerebellar ataxia, frontotemporal
degeneration, Huntington disease, Parkinson disease, cognitive
impairment, aphasia and oculomotor apraxia. Quantitatively, the extent
of the viral octapeptide sharing with neurodegeneration-associated
proteins is in excess when analyzed in a stochastic expectation context.
Qualitatively, two main features characterize the peptide matching: 1)
many common sequences are single amino acid repeats, and 2) mostly, the
shared octapeptides are part of experimentally validated epitopes, thus
suggesting an immune crossreactive potential of the viral peptides
shared with brain antigens involved in neurodegeneration. The present
study may have relevance for peptide-based therapeutic approaches to
block potential autoimmune crossreactions in neurological diseases and
dysfunctional behavior.

Alzheimer’s disease: APP, gamma secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, MS4A2, herpes simplex, C.pneumoniae and immunity

The major susceptibility genes identified in Alzheimer’s disease genome-wide association studies (APOE, ABCA7, BIN1, CLU, CD2AP, CD33, CR1, EPHA1, MS4A2 and PICALM), as well as APP and gamma-secretase are involved in the herpes simplex life cycle, or in that of other suspect pathogens (C.Pneumoniae, H.Pylori, C.Neoformans, B. Burgdorferri and P.Gingivalis) or in immune defence. As several of these pathogens can promote beta-amyloid deposition and tau phosphorylation in non-transgenic models, they might be considered as causative agents in the human condition, whose effects are tempered by susceptibility genes. Beta-amyloid is an antimicrobial peptide, and APP and gamma-secretase are highly expressed in dendritic cells, the scouts that present pathogen antigens to immunocompetent cells. Gamma secretase cleaves 21 viral or microbial receptors, including those for the suspect pathogens and the primary role of the amyloid/secretase network may well be related to pathogen disposal, effects which may be abrogated by the presence of beta-amyloid autoantibodies in the elderly. These autoantibodies, as well as those to nerve growth factor and tau, also observed in Alzheimer’s disease, may well in fact be antibodies to pathogens, as there exists a marked homology between the human autoantigens and pathogen proteins. Antibodies to NGF or tau promote beta-amyloid deposition, neurofibrillary tangles or cholinergic neuronal loss, and, with other autoantibodies, such as anti-ATPase, they are potential agents of destruction, whose formation is dictated by sequence homology between pathogen and human proteins, and thus by pathogen strain and human genes. The regular detection and elimination of pathogens in the ageing population might impact significantly upon the incidence of Alzheimer’s disease, and the early selective removal of culpable autoantibodies might offer hope for a cure. Tweet 

Extensive viral mimicry of 22 AIDS related autoantigens by HIV-1 proteins and pathway analysis of 561 viral/human homologues suggest an initial treatable autoimmune component of AIDS.

The autoantibodies seen in HIV-1/AIDS target many members of the immune network and the autoantigens are homologous to viral proteins: Antibodies raised to the virus may target the immune system because of this mimicry.
Genes and other pathogens affecting the progression of AIDS

Yellow Fever Vaccination and Increased Relapse Rate in Travelers With Multiple Sclerosis.

Yellow fever vaccination was associated with an almost 12 fold increase  in relapse rate in multiple sclerosis patients.

Multiple sclerosis risk factors


 

Charting the peptide crossreactome between HIV-1 a... [Front Biosci (Elite Ed). 2011] - PubMed result

The HIV-1 proteome shares extensive homology with human proteins, including those involved in AIDS, or with the comorbid conditions associated with AIDS (psychosis, myopathy, cardiovascular disorders, hypertension, corneal diseases, diarrhea, lymphoma, and bladder cancer).

The findings are relevant to HIV-1 escape from immune surveillance, adjuvant-induced HIV-1 immunogenicity, and autoimmune cross-reactivity following human hyperimmune responses against HIV-1, and AIDS.

This phenomenon is also common to other viruses and bacteria, whose proteins resemble those relevant to the pathologies of the diseases in which they are implicated - for example herpes simplex and Alzheimer's disease, or diverse pathogens and schizophrenia.

Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes

Autoimmune bullous diseases The spectrum of infectious agent antibodies and review of the literature.

Pemphigus and bullous pemphigoid are autoimmune diseases that have have a genetic predisposition which promotes the production of auto-antibodies targeted against components of the epidermal desmosome and hemidesmosome. 
This study suggests a contributing role for Hepatitis B and hepatitis C,  H. pylori, T. gondii and the cytomegalovirus in inducing autoimmune bullous disease in genetically susceptible individuals.

Could antibodies raised to these infectious agents cross react with the autoantigens ?

Endogenous bornavirus elements in mammalian genome

Many other non-retroviral viral elements are also found in human genomes Refs The bornavirus has also been impicated in bipolar disorder

Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997-2002.

This study showed that in male children, hepatitis B vaccination was associated with a three fold higher risk of  their parents reporting autism

  Risk factors:  Autism :   Kegg pathways in autism 

A set of papers showing viral integration into plant, arthropod, fungal, nematode, and protozoan, mammalian and human genomes

 Viral integration into the human genome had until recently been thought to be the preserve of retroviruses. It is now clear that non retroviruses, both RNA viruses and DNA viruses, have also been inserted over evolutionary time , and that this is an ongoing process. This would appear to be the driving force in evolution.

The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro

The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro

See also this set of papers 

A DISC1/Viral interactome

HIV-1 Image via Wikipedia

Viral (see BLASTS) and these papers from Kanduc's lab,  and bacterial proteins (Trost et al, 2010) show extensive homology (pentapeptides or more) with all human proteins: Because of this , they are able to mimic or block the actions of their human counterparts and compete with their binding partners in interactomes. DISC1 is no exception and an example of viruses that bind to DISC1 binding partners is shown here. Many interactomes will be disrupted by viruses - there are over 1000 HIV-1/host interactions in the HIV-1/host interaction database at NCBI and nearly 400 in the herpes simplex/host database, and about 2,500 different viruses . The same goes for bacteria and other pathogens. In effect, pathogens become a part of our signalling networks and this is one way in which they contribute to diseases.

Risk factors:  Schizophrenia  
Kegg pathways  Schizophrenia Herpes simplex infection

Endogenous Viral Etiology of Prion Diseases : Nature Precedings

 

When the human viral infectome and diseasome networks collide: towards a systems biology platform for the aetiology of human diseases.

Viruses interact with many human proteins, and in doing so interfere with signalling networks and interactomes. This in silico analysis involved 110 viruses and uncovered several disease-relevant pathways. Viruses are risk factors in most human diseases, and this type of analysis will help to explain how and why. Very important.


For example :  Herpes simplex infection pathways

Search Amazon.com for host pathogen 

A database of multiple sclerosis environmental risk factors

 This is a referenced dataset of some of the risk and protective factors associated with multiple sclerosis. There is much debate about the relevance of many of these, but their listing together may help to make sense of the puzzle. Risk factors may act together and with genes , either increasing or decreasing the degree of risk.

Search Amazon.com for multiple sclerosis

The incidence of psychotic disorders varies greatly across places and demographic groups

The distibution of negative and positive association data also varies according to geographical localisation and tends to cluster in hot and cold spots around the globe as shown here . Part of this is due to population genetics (polymorphisms have a single ancestral root and arise in a particular place at a particular time) . Some of this effect may also relate to the similarity between viral genes and susceptibility genes. In other words, some genetic studies have been tracking infection as well as identifying candidate genes.

MHC2TA rs4774C and HHV-6A active replication in multiple sclerosis patients.

HHV-6
multiple sclerosis

An N-terminally truncated envelope protein encoded by a human endogenous retrovirus W locus on chromosome Xq22.3.

Detection of an antigen by 6A2B2 in placenta and multiple sclerosis lesions opens the possibility that N-Trenv could be expressed in vivo