The viruses in your blood

blood bagIf you have ever received a blood transfusion, along with the red blood cells, leukocytes, plasma and other components, you also were infused with a collection of viruses. A recent study of the blood virome of over 8,000 healthy individuals revealed 19 different DNA viruses in 42% of the subjects.

Viral DNA sequences were identified among the genome sequences of 8,240 individuals that were determined from blood. Of the 1 petabyte (1 million gigabytes) of sequence data that were generated, about 5% did not correspond to human DNA. Within this fraction, sequences of 94 different viruses were identified. Nineteen of these were human viruses. The method is not expected to reveal RNA viruses except retroviruses which are integrated as DNA copies in the host chromosomes.

The most common human viruses identified were herpesviruses, including cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and human herpesvirus 7 and 8, found in 14-20% of individuals. Anelloviruses, small viruses with a circular genome, were found in 9% of the samples. Other viruses found in less than 1% of the samples included papillomaviruses, parvoviruses, polyomavirus, adenovirus, human immunodeficiency virus and human T-lymphotropic virus (the latter two integrated into the host DNA).

The other 75 viruses are likely contaminants from laboratory reagents or from the environment. These include sequences from non-human retroviruses, four different giant DNA viruses, and a virus of bees, all found in less than 10 samples. These findings illustrate the challenge in distinguishing bona fide human viruses from contaminants.

Identifying viruses in blood is an important objective for ensuring the safety of the blood supply. Donor blood is currently screened for HIV-1 and 2, human T-lymphotropic virus-1 and 2, hepatitis C virus, hepatitis B virus, West Nile virus, and Zika virus. These viruses are pathogenic for humans and can be transmitted via the blood. Some viruses, such as anelloviruses and pegiviruses, are in most donated blood, yet their pathogenic potential is unknown. It is not feasible to reject donor blood that contains any type of viral nucleic acid – if we did, we would not have a blood supply.

Continuing studies of the blood virome are needed to define which viruses should be tested for in donated blood. The human papillomavirus (17 people), Merkel cell polyomavirus (49 people), HHV8 (3 people) and adenovirus (9 people) detected in this study could be transmitted in the blood and their presence should be monitored in future studies.

It’s important to emphasize that this work describes only viral DNA sequences, not infectious viruses. The blood supply is screened by nucleic acid tests, but it is important to determine if infectious virus is also present. If viral DNA is present in blood but infectious virus is never found, then it might not be necessary to reject blood based on the presence of certain sequences.

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TWiV 433: Poops viruses and worms

The lovely TWiV team explore evolution of our fecal virome, and the antiviral RNA interference response in the nematode C. elegans.

You can find TWiV #433 at microbe.tv/twiv, or listen below.

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TWiV 405: All the world’s a phage

The TWiXers discuss a study on vertical transmission of Zika virus by Aedes mosquitoes, and uncovering Earth’s virome by mining existing metagenomic sequence data.

You can find TWiV #405 at microbe.tv/twiv, or listen below.

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TWiV 391: Whiter reefs, fresh breath

If you have always wanted to know what coral reefs and the human oral cavity have in common, listen as guests David Pride and Forest Rohwer talk about their work on the microbiomes and viromes of these two environments, and you’ll also understand why mucus is cool.

You can find TWiV #391 at microbe.tv/twiv, or watch or listen below.

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TWiV 370: Ten out of 15

On episode #370 of the science show This Week in Virology, the TWiVomics review ten captivating virology stories from 2015.

You can find TWiV #370 at www.microbe.tv/twiv.

TWiV 362: Gotta catch ’em all

On episode #362 of the science show This Week in Virology, the virus virtuosos, with their usual verve, illuminate a new method to identify all the viral nucleic acids in a sample, and regulation of viral gene expression by codon usage.

You can find TWiV #362 at www.microbe.tv/twiv.

TWiV 355: Baby’s first virome

On episode #355 of the science show This Week in Virology, the TWiV team considers the effect of a Leishmaniavirus on the efficacy of drug treatment, and the human fecal virome and microbiome in twins during early infancy.

You can find TWiV #355 at www.microbe.tv/twiv.

The Arctic fresh water virome

SpitsbergenAlthough we now understand that viruses are the most abundant organisms on Earth, there are gaps in our knowledge about their distribution in different environments. Results of a new study reveal the diversity and distribution of viruses in Arctic fresh waters.

Fresh waters in high latitudes such as the Arctic and Antarctic have low levels of nutrients (e.g. are oligotrophic) and support the growth mainly of microorganisms. They are good model systems for understanding how viruses affect microbial communities and the entire ecosystem. It is known that diverse viral communities, comprising novel families of single-stranded (ss) DNA viruses, dominate the fresh waters of the Antarctic Lake Limnopolar. However no large scale studies of the Arctic fresh water virome have been done.

Fresh water was collected in three different years from six lakes in Spitsbergen, Norway (red symbol on map). Viral particles were purified from the water samples and their genome sequences were determined. Only about 10% of the viral sequences could be assigned to a previously known virus family. Most (86%) of the recognizable sequences were from ssDNA viruses, and similar viruses were found in all six lakes.

Comparisons with viromes from other freshwater locations revealed similar taxonomic distributions in Antarctic freshwater but not elsewhere. As these locations are at opposite ends of the global poles, the results suggest that some viruses may be dispersed over long distances. The Arctic and Antarctic fresh water viromes do contain different viral species, despite being quite similar environments. On the other hand, the Arctic fresh water virome is very different from the Arctic Ocean virome. The finding of diverse viral communities in Arctic and Antarctic fresh waters indicates that, unlike larger organisms, viral richness might not decrease with distance from the equator.

The authors of this study did not characterize the RNA virome of Arctic fresh water lakes, but they did find sequences of single-stranded RNA viruses in their data sets. Because the authors sequenced DNA only (their protocol did not include a step to convert RNA to DNA before amplification), these RNA viral sequences likely represent DNA-RNA hybrid viruses. These viruses probably were produced by recombination of a DNA virus with DNA produced by reverse transcription of an RNA virus.

When Lake Limnopolar thaws in the spring, its viral community changes from ssDNA viruses to dsDNA viruses, perhaps as the hosts also change. Whether similar changes take place in Spitsbergen should be determined to help illuminate how viruses control high latitude microbial communities.

TWiV 342: Public epitope #1

On episode #342 of the science show This Week in Virology, the TWiVniks discuss the structure of a virus that reproduces in an extreme environment, long-term consequences of Ebolavirus infection, and VirScan, a method to identify the different virus infections you have had in your lifetime.

You can find TWiV #342 at www.microbe.tv/twiv.

Your viral past

virusesDid you ever wonder what different virus infections you have had in your lifetime? Now you can find out with just a drop of your blood and about $25.

Immune defense systems of many hosts produce antibodies in response to virus infections. These large proteins, which are generally virus specific, can block or inhibit virus infection, and persist at low levels for many years after the initial infection. Hence it is possible to determine whether an individual has had a virus infection by looking for anti-viral antibodies in the blood. Up to now the process of identifying such antibodies has been slow and limited to one or a few viruses. A new assay called VirScan allows unbiased searches for all the virus antibodies in your blood, providing a picture of all your past infections.

To identify the human antivirome, DNAs were synthesized encoding proteins from all viruses known to infect humans – 206 species and over 1000 strains. These DNAs were inserted into the genome of a bacteriophage, so that upon infecting bacteria, the viral peptides are displayed on the phage capsid. These ‘display’ phages were then mixed with human serum, and those that were bound by antibodies were isolated. The DNA sequence of the phage genomes were then determined to identify the human virus bound by the antibodies.

This method was used to assay samples from 569 humans. The results show that each person had been exposed to an average of 10 viruses, with a range from a few to over 20 (two individuals had antibodies to 84 different virus species!). The most frequently identified viruses included herpesviruses, rhinoviruses, adenoviruses, influenza viruses, respiratory syncytial virus, and enteroviruses. The overall winner, found in 88% of samples, is Epstein-Barr virus.

These results are not unexpected: all of us are infected with at least a dozen viruses at any time, and the viruses identified in this study known to infect much of the human population. What was surprising is the absence of some common viruses, such as rotaviruses, and the ubiquitous polyomaviruses. According to serological surveys, the most common human viruses are the small, single-stranded DNA containing anelloviruses. Yet the related torque teno virus was only found in 1.7% of samples. These differences are likely due to a combination of technical and biological issues (e.g., failure of antibodies to certain viruses to persist in serum).

This new assay may one day become a routine diagnostic tool that is used along with complete blood counts and chemistries to know if a patient’s signs and symptoms might be attributable to a past virus infection. VirScan technology is not limited to virus infections – it can be used to provide a history of bouts with bacteria, fungi, and parasites.

VirScan might also allow us to determine which virus infections are beneficial, and which contribute to chronic diseases such as autoimmune or neurodevelopmental disorders or cancer. The assay can be used to conduct unbiased population-based studies of the prevalence of virus infections and their possible association with these diseases. Such connections were not previously possible with antibody assays that search for one virus at a time. This approach was not only inefficient, but required guessing the responsible virus.

Some other findings of this study are noteworthy. As expected, children had fewer virus infections than adults. HIV-positive individuals had antibodies to more viruses than HIV-negative individuals, also expected given the damage done by this virus to the immune system. Frequencies of anti-viral antibodies were higher outside of the United States, possible due to differences in genetics, sanitation, or population density. In most samples, there was a single dominant peptide per virus, although there were occasional differences among populations. This information might be useful for improving vaccines, or tailoring them to specific countries or regions.

Update: It would be very informative to use VirScan to search for antibodies against viruses that are not known to infect humans. Other animal viruses, plant viruses, insect viruses: to which do a significant fraction of humans respond? The information might identify other viruses that replicate in humans and which might constitute future threats (or present benefits).