Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

 "Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease."



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The blood DNA virome in 8,000 humans

 The characterization of the blood virome is important for the safety of blood-derived transfusion products, and for the identification of emerging pathogens. We explored non-human sequence data from whole-genome sequencing of blood from 8,240 individuals, none of whom were ascertained for any infectious disease. Viral sequences were extracted from the pool of sequence reads that did not map to the human reference genome. Analyses sifted through close to 1 Petabyte of sequence data and performed 0.5 trillion similarity searches. With a lower bound for identification of 2 viral genomes/100,000 cells, we mapped sequences to 94 different viruses, including sequences from 19 human DNA viruses, proviruses and RNA viruses (herpesviruses, anelloviruses, papillomaviruses, three polyomaviruses, adenovirus, HIV, HTLV, hepatitis B, hepatitis C, parvovirus B19, and influenza virus) in 42% of the study participants. Of possible relevance to transfusion medicine, we identified Merkel cell polyomavirus in 49 individuals, papillomavirus in blood of 13 individuals, parvovirus B19 in 6 individuals, and the presence of herpesvirus 8 in 3 individuals. The presence of DNA sequences from two RNA viruses was unexpected: Hepatitis C virus is revealing of an integration event, while the influenza virus sequence resulted from immunization with a DNA vaccine. Age, sex and ancestry contributed significantly to the prevalence of infection. The remaining 75 viruses mostly reflect extensive contamination of commercial reagents and from the environment. These technical problems represent a major challenge for the identification of novel human pathogens. Increasing availability of human whole-genome sequences will contribute substantial amounts of data on the composition of the normal and pathogenic human blood virome. Distinguishing contaminants from real human viruses is challenging.



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Redefining the invertebrate RNA virosphere : Nature : Nature Research

"Current knowledge of RNA virus biodiversity is both biased and fragmentary, reflecting a focus on culturable or disease-causing agents. Here we profile the transcriptomes of over 220 invertebrate species sampled across nine animal phyla and report the discovery of 1,445 RNA viruses, including some that are sufficiently divergent to comprise new families. The identified viruses fill major gaps in the RNA virus phylogeny and reveal an evolutionary history that is characterized by both host switching and co-divergence. The invertebrate virome also reveals remarkable genomic flexibility that includes frequent recombination, lateral gene transfer among viruses and hosts, gene gain and loss, and complex genomic rearrangements. Together, these data present a view of the RNA virosphere that is more phylogenetically and genomically diverse than that depicted in current classification schemes and provide a more solid foundation for studies in virus ecology and evolution."



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Scientists triple known types of viruses in world's oceans

The world's oceans teem with scientific mystery, unknowns that could prove to be tools that will one day protect the planet from global warming.

An international research team now reports they've tripled the known types of viruses living in waters around the globe and have a better idea what role they play in nature. Led by Ohio State University scientists, the team includes University of Michigan biologist Melissa Duhaime.

The oceans currently soak up half of that carbon, but that comes at the cost of acidifying the oceans, which puts some ocean-dwellers, including shellfish, at risk. Understanding how microbes and viruses interact is critical to any possible management efforts, the researchers said.

90 percent of skin-based viruses represent unknown viral 'dark matter,' scientists reveal -- ScienceDaily

"Scientists in recent years have made great progress in characterizing the bacterial population that normally lives on human skin and contributes to health and disease. Now researchers have used state-of-the-art techniques to survey the skin's virus population, or "virome." The study reveals that most DNA viruses on healthy human skin are viral "dark matter" that have never been described before. The research also includes the development of a set of virome analysis tools that are now available to researchers for further investigations."



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Test detects all viruses that infect you and your pet - Futurity

A new test called ViroCap can detect thousands of viruses that make people and animals sick.

The test is as sensitive as the gold-standard laboratory tests—called polymerase chain reaction (PCR) assays. However, even the most expansive PCR assays can only screen for up to about 20 similar viruses at the same time. ViroCap looks for everything.

“With this test, you don’t have to know what you’re looking for,” says Gregory Storch, a professor of pediatrics at Washington University School of Medicine in St. Louis. “It casts a broad net and can efficiently detect viruses that are present at very low levels. We think the test will be especially useful in situations where a diagnosis remains elusive after standard testing or in situations in which the cause of a disease outbreak is unknown.”

Here's the paper:-

Enhanced virome sequencing through solution-based capture enrichment

Related articles

• Viruses from newborn gut are new to science

Viral metagenomics in drug-naïve, first-onset schizophrenia patients with prominent negative symptoms. - PubMed - NCBI

Although several studies suggest a virus or (endogenous) retrovirus involvement at the time of onset of schizophrenia, the unequivocal identification of one or more infectious agents, by means of an undirected catch-all technique, has never been conducted. In this study VIDISCA, a virusdiscovery method, was used in combination with Roche-454 high-throughput sequencing as a tool to determine the possible presence of viruses (known or unknown) in blood of first-onset drugs-naïve schizophrenic patients with prominent negative symptoms. Two viruses (the Anellovirus Torque Teno virus and GB virus C) were detected. Both viruses are commonly found in healthy individuals and no clear link with disease was ever established. Viruses from the family Anelloviridae were also identified in the control population (4.8%). Besides, one patient sample was positive for human endogenous retroviruses type K (HML-2) RNA but no specific predominant strain was detected, instead 119 different variants were found. In conclusion, these findings indicate no evidence for viral or endogenous retroviral involvement in sera at the time of onset of schizophrenia.

Comprehensive serological profiling of human populations using a synthetic human virome

Introduction The collection of viruses found to infect humans can have profound effects on human health. In addition to directly causing acute or chronic illness, viral infection can alter host immunity in more subtle ways, leaving an indelible footprint on the immune system. This interplay between virome and host immunity has been implicated in the pathogenesis of complex diseases such as type 1 diabetes, inflammatory bowel disease, and asthma. Despite the growing appreciation for the importance of interactions between the virome and host, a comprehensive method to systematically characterize these interactions has yet to be developed.
Rationale Current serological methods to detect viral infections are predominantly limited to testing one pathogen at a time and are therefore used primarily to address specific clinical hypotheses. A method that could simultaneously detect responses to all human viruses would allow hypothesis-free analysis to detect associations between past viral infections and particular diseases or population structures. Humoral responses to infection typically arise within 10 to 14 days of initial exposure and can persist over years or decades, thus providing a rich source of the history of pathogen encounters. In this work, we present VirScan, a high-throughput method that allows comprehensive analysis of antiviral antibodies in human sera. VirScan uses DNA microarray synthesis and bacteriophage display to create a uniform, synthetic representation of peptide epitopes comprising the human virome. Immunoprecipitation and high-throughput DNA sequencing reveal the peptides recognized by antibodies in the sample. The analysis requires less than 1 μl of blood. Results We screened sera from 569 human donors across four continents, assaying a total of over 108 antibody-peptide interactions for reactivity to 206 human viral species and >1000 strains. We found that VirScan’s performance in detecting known infections and distinguishing between exposures to related viruses is comparable to that of classical serum antibody tests for single viruses. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Our approach maps antibody targets at 56–amino acid resolution, and our results nearly double the number of previously established viral B cell epitopes. Although rates of specific virus exposure varied depending on age, HIV status, and geographic location of the donor, we observed strong similarities in antibody responses across individuals. In particular, we found multiple instances of single peptides that were recurrently recognized by antibodies in the vast majority of donors. We performed tiling mutagenesis and found that these antibody responses targeted substantially conserved “public epitopes” for each virus, suggesting that antibodies with highly similar specificities, and possibly structures, are elicited across individuals.
Conclusion VirScan is a method that enables human virome-wide exploration, at the epitope level, of immune responses in large numbers of individuals. We have demonstrated its effectiveness for determining viral exposure and characterizing viral B cell epitopes in high throughput and at high resolution. Our preliminary studies have revealed intriguing general properties of the human immune system, both at the individual and the population scale. VirScan may prove to be an important tool for uncovering the effect of host-virome interactions on human health and disease and could easily be expanded to include new viruses as they are discovered, as well as other human pathogens, such as bacteria, fungi, and protozoa.

Comprehensive serological profiling of human populations using a synthetic human virome

Introduction 
The collection of viruses found to infect humans can have profound effects on human health. In addition to directly causing acute or chronic illness, viral infection can alter host immunity in more subtle ways, leaving an indelible footprint on the immune system. This interplay between virome and host immunity has been implicated in the pathogenesis of complex diseases such as type 1 diabetes, inflammatory bowel disease, and asthma. Despite the growing appreciation for the importance of interactions between the virome and host, a comprehensive method to systematically characterize these interactions has yet to be developed.
Rationale
 Current serological methods to detect viral infections are predominantly limited to testing one pathogen at a time and are therefore used primarily to address specific clinical hypotheses. A method that could simultaneously detect responses to all human viruses would allow hypothesis-free analysis to detect associations between past viral infections and particular diseases or population structures. Humoral responses to infection typically arise within 10 to 14 days of initial exposure and can persist over years or decades, thus providing a rich source of the history of pathogen encounters. In this work, we present VirScan, a high-throughput method that allows comprehensive analysis of antiviral antibodies in human sera. VirScan uses DNA microarray synthesis and bacteriophage display to create a uniform, synthetic representation of peptide epitopes comprising the human virome. Immunoprecipitation and high-throughput DNA sequencing reveal the peptides recognized by antibodies in the sample. The analysis requires less than 1 μl of blood.
Results
 We screened sera from 569 human donors across four continents, assaying a total of over 108 antibody-peptide interactions for reactivity to 206 human viral species and >1000 strains. We found that VirScan’s performance in detecting known infections and distinguishing between exposures to related viruses is comparable to that of classical serum antibody tests for single viruses. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Our approach maps antibody targets at 56–amino acid resolution, and our results nearly double the number of previously established viral B cell epitopes. Although rates of specific virus exposure varied depending on age, HIV status, and geographic location of the donor, we observed strong similarities in antibody responses across individuals. In particular, we found multiple instances of single peptides that were recurrently recognized by antibodies in the vast majority of donors. We performed tiling mutagenesis and found that these antibody responses targeted substantially conserved “public epitopes” for each virus, suggesting that antibodies with highly similar specificities, and possibly structures, are elicited across individuals.
Conclusion 
VirScan is a method that enables human virome-wide exploration, at the epitope level, of immune responses in large numbers of individuals. We have demonstrated its effectiveness for determining viral exposure and characterizing viral B cell epitopes in high throughput and at high resolution. Our preliminary studies have revealed intriguing general properties of the human immune system, both at the individual and the population scale. VirScan may prove to be an important tool for uncovering the effect of host-virome interactions on human health and disease and could easily be expanded to include new viruses as they are discovered, as well as other human pathogens, such as bacteria, fungi, and protozoa.

Reduced maternal levels of common viruses during pregnancy predict offspring psychosis: Potential role of enhanced maternal immune activity? - PubMed - NCBI

Viral infections during the prenatal or early childhood periods are one
of the environmental factors which might play an etiological role in
psychoses. Several studies report higher antibody levels against viruses
during pregnancy in blood of mothers of offspring with psychotic
disorders, but the presence of such viruses has never been demonstrated.
The goal of this study was to investigate the potential association
between viral infections during pregnancy and progeny with psychotic
disorders and, for this purpose, we performed a nested case-control
study involving pregnant mothers of offspring with schizophrenia or
bipolar disorder with psychotic features (cases, N=43) and pregnant
women with healthy offspring (controls, N=95). Since several potential
viral candidates have been suggested in prior work, a broad-spectrum
virus detection system was necessary. A metagenomic analysis performed
with the virus discovery method VIDISCA-454 revealed only common
blood-associated viruses in all cohorts. However, a significantly lower
viral prevalence was detected in the group of cases and in the
sub-population of pregnant mothers of offspring with schizophrenia
(p<0.05). Consistent with the existing inverse correlation between
the level of these viruses and the immunocompetence of an individual, we
hypothesized the presence of a higher immune activity during pregnancy
in mothers whose offspring later develop a psychotic disorder as
compared to controls. Combining our results with previously available
literature data on antibody levels during the gestation period suggests
that a more prominent maternal immune activity can be considered a risk
factor for developing psychosis.

Viral Virtuosos | The Scientist Magazine®

A diverse, abundant, and underappreciated viral community exists on and within us, from our skin to our eyes, blood, brain, and other organs—even within our own genomes.1 Unlike marauding Ebola-like viruses, these viruses establish a balanced coexistence that can persist for a host’s entire lifetime. This coexistence involves careful control of the viral life cycle: whereas Ebola virus infection is flashy, persistent infection is elegant.

Among other challenges, persistent viruses must effectively subvert the host immune response. To accomplish this, these viruses control both the timing and amount of viral replication. Such nuanced infectious cycles involve carefully choreographed viral gene expression that can foster completely different lifestyles depending on host cell type, cell-signaling events, or other factors. One important class of regulators that helps to mediate these lifestyle switches is the noncoding regulatory RNAs (ncRNAs), which today stand at the center of an ongoing mini-revolution in our understanding of gene-expression control.

Previously thought of as a simple decoder of genetic information—serving as an intermediate between DNA and protein—RNA is now known to engage in a bevy of other important biochemical activities. Despite differences in ncRNA sequence, size, and function, a theme is emerging: diverse biological processes rely on ncRNAs to balance the timing and magnitude of gene expression.2 In eukaryotes, microRNAs (miRNAs) represent the best-characterized ncRNAs. About 22 nucleotides in length, these small RNAs bind to and repress target messenger RNA (mRNA) transcripts, allowing for fine-tuning of gene expression. The human genome encodes hundreds of different miRNAs to regulate numerous biological functions, and recent research is revealing how the viruses of the human body use these miRNAs, as well as their own, to establish and maintain long-term persistent infections.

Viruses may play unexpected role in inflammatory bowel diseases

"Inflammatory bowel diseases are associated with a decrease in the diversity of bacteria in the gut, but a new study led by researchers at Washington University School of Medicine in St. Louis has linked the same illnesses to an increase in the diversity of viruses.

The scientists found that patients with inflammatory bowel diseases had a greater variety of viruses in their digestive systems than healthy volunteers, suggesting viruses likely play a role in the diseases"

Healthy humans make nice homes for viruses Washington University in St. Louis

On average, healthy individuals carry about five types of viruses on their bodies, the researchers report online in BioMed Central Biology. The study is the first comprehensive analysis to describe the diversity of viruses in healthy people.

The research was conducted as part of the Human Microbiome Project, a major initiative funded by the National Institutes of Health (NIH) that largely has focused on cataloging the body’s bacterial ecosystems.
Analyzing the samples, the scientists found seven families of viruses, including strains of herpes viruses that are not sexually transmitted. For example, herpesvirus 6 or herpesvirus 7 was found in 98 percent of individuals sampled from the mouth. Certain strains of papillomaviruses were found in about 75 percent of skin samples and 50 percent of samples from the nose. Novel strains of the virus were found in both sites.
Not surprisingly, the vagina was dominated by papillomaviruses, with 38 percent of female subjects carrying such strains. Some of the women harbored certain high-risk strains that increase the risk of cervical cancer. These strains were more common in women with communities of vaginal bacteria that had lower levels of Lactobacillus and an increase in bacteria such as Gardnerella, which is associated with bacterial vaginosis.
Adenoviruses, the viruses that cause the common cold and pneumonia, also were common at many sites in the body.

Metagenomic analysis of double-stranded DNA viruses in healthy adults.

The Human Microbiome Project (HMP) was undertaken with the
goal of defining microbial communities in and on the bodies of healthy
individuals using high-throughput, metagenomic sequencing analysis. The
viruses present in these microbial communities, the `human virome¿, are
an important aspect of the human microbiome that is particularly
understudied in the absence of overt disease. We analyzed eukaryotic
double-stranded DNA (dsDNA) viruses, together with dsDNA replicative
intermediates of single-stranded DNA viruses, in metagenomic sequence
data generated by the HMP. 706 samples from 102 subjects were studied,
with each subject sampled at up to five major body habitats: nose, skin,
mouth, vagina, and stool. Fifty-one individuals had samples taken at
two or three time points 30 to 359 days apart from at least one of the
body habitats.ResultsWe detected an average of 5.5 viral genera in each
individual. At least 1 virus was detected in 92% of the individuals
sampled. These viruses included herpesviruses, papillomaviruses,
polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and
circoviruses. Each individual had a distinct viral profile,
demonstrating the high interpersonal diversity of the virome. Some
components of the virome were stable over time.ConclusionsThis study is
the first to use high-throughput DNA sequencing to describe the
diversity of eukaryotic dsDNA viruses in a large cohort of normal
individuals who were sampled at multiple body sites. Our results show
that the human virome is a complex component of the microbial flora.
Some viruses establish long-term infections that may be associated with
increased risk or possibly with protection from disease. A better
understanding of the composition and dynamics of the virome may hold
important keys to human health.

The vast virome | Science News

Scientists estimate that 10 quintillion virus particles populate the planet. That’s a one followed by 31 zeros. They outnumber bacteria 10-to-1 in most ecosystems. And they’re ubiquitous in and on humans.

Pérez-Brocal and others are learning that viruses, once seen only as foreign invaders that make people sick, are an integral part of human biology. Some cause major diseases, including influenza, AIDS and some cancers. Others, conversely, may promote health. Some may even help us gauge how well the human immune system works.

The study of people’s resident viruses, known collectively as the human virome, is “a whole new frontier in the understanding of humans,” and could become important for the future of medicine, says Forest Rohwer, an environmental microbiologist at San Diego State University.

Rohwer’s research indicates that viruses are part of the human defense system. Mucus studded with bacteria-infecting viruses called bacteriophage, or phage, may help protect host cells from invasive microbes, he and his colleagues reported June 25 in the Proceedings of the National Academy of Sciences (SN Online: 5/20/13). Within the mucus barrier that lines airways and intestines and coats the mouth and other orifices, the host and phage conspire to control the movement of bacteria. Anchored to sugars produced by host cells, phage infect and blow up invading bacteria that try to cross the mucus barrier.

As scientists take a census of the virome, they’ve begun to reveal these kinds of unexpected partnerships, but the work lags far behind that of the rest of the microbiome.

Cell - Temporal Response of the Human Virome to Immunosuppression and Antiviral Therapy

There are few substantive methods to measure the health of the immune system, and the connection between immune strength and the viral component of the microbiome is poorly understood. Organ transplant recipients are treated with posttransplant therapies that combine immunosuppressive and antiviral drugs, offering a window into the effects of immune modulation on the virome. We used sequencing of cell-free DNA in plasma to investigate drug-virome interactions in a cohort of organ transplant recipients (656 samples, 96 patients) and find that antivirals and immunosuppressants strongly affect the structure of the virome in plasma. We observe marked virome compositional dynamics at the onset of the therapy and find that the total viral load increases with immunosuppression, whereas the bacterial component of the microbiome remains largely unaffected. The data provide insight into the relationship between the human virome, the state of the immune system, and the effects of pharmacological treatment and offer a potential application of the virome state to predict immunocompetence.

Scientists estimate that there is a minimum of 320,000 viruses in mammals awaiting discovery.

To address the challenges of describing and estimating virodiversity, a team of investigators from CII and EcoHealth Alliance began in jungles of Bangladesh—home to the flying fox.  These bats are the largest flying mammal with a wingspan of up to 6 feet; they are also the source of several outbreaks of Nipah virus. The team collected 1,897 biological samples from the animals, which were captured and released. Back in the lab, they used polymerase chain reaction to identify 55 viruses in nine viral families. Of these, only five were previously known, including two human bocaviruses, an avian adenovirus, a human/bovine betacoronavirus, and an avian gammacoronavirus. Another 50 were newly discovered, including 10 in the same family as Nipah. Next the researchers adapted a statistical technique from the field of ecology to estimate that there were another three rare viruses unaccounted for in the samples, upping the estimate of viruses in the flying fox to 58. Finally, this number was extrapolated to all 5,486 known mammals, yielding a total of at least 320,000 viruses.

The other microbiome–exploring the human virome | National Academy of Sciences

In June 2012, scientists around the world simultaneously published a series of papers spearheaded by the US National Institutes of Health’s Human Microbiome Project (HMP) that characterized the fundamentals of the microbiome in healthy individuals (3). By definition, the microbiome includes all microbes in the human body: bacteria, viruses, and fungi. Most initial HMP research, however, focused on bacteria because there is a standardized and thorough protocol for isolating and characterizing bacterial genes from the slurry of DNA in human feces or saliva swabs. Viruses, in contrast, have so far been the forgotten siblings of the microbiome family. But a growing cadre of researchers argues that the human virome is probably at least as important to human health as our bacterial inhabitants.

SIV and the Expanding Virome - The Scientist Magazine®

Pathogenic infection with simian immunodeficiency virus (SIV), a relative of HIV that infects non-human primates, is associated with increased diversity of gastrointestinal virus species in rhesus macaques, according to findings published today (October 11) in Cell. Though previous work has implicated intestinal bacteria in stimulating chronic inflammation, which is believed to promote progression from HIV or SIV infection to AIDS, the new findings suggest that gut viruses may also play a role.