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).

TWiV 323: A skid loader full of viromes

On episode #323 of the science show This Week in Virology, the family TWiVidae discuss changes in the human fecal virome associated with Crohn’s disease and ulcerative colitis.

You can find TWiV #323 at www.microbe.tv/twiv.

TWiV 315: Must be something in the water

On episode #315 of the science show This Week in Virology, Vincent, Alan, Rich and Kathy discuss the association of a virus with sea star melting disease, and the finding of a phycodnavirus in the oropharynx of humans with altered cognitive functions.

You can find TWiV #315 at www.microbe.tv/twiv.

TWiV 313: With viruses like these, who needs enemas?

On episode #313 of the science show This Week in Virology, Vincent, Alan, and Rich discuss how norovirus, an enteric virus, can replace the functions of the gut microbiome.

You can find TWiV #313 at www.microbe.tv/twiv.

Algal virus associated with altered human cognitive functions

Phycodnaviridae virionMany well-known human viruses, including poliovirus, rabies virus, West Nile virus, can infect cells of the nervous system, leading to alterations in the function of that organ. Could a virus that infects algae also cause human neurological alterations?

Chloroviruses are large DNA-containing viruses that infect unicellular algae called zoochlorellae (pictured: image credit, ViralZone). Unexpectedly, chlorovirus DNA sequences were found in the oropharynx of 40 of 92 individuals (43.5%) who had no known physical or psychiatric illness. The clinical specimens had been obtained as part of a study of cognitive function, and it was possible to determine that presence of chlorovirus DNA was associated with a slight but statistically significant decreased performance in tests for visual motor speed, delayed memory, and attention.

When mice were fed chlorovirus-infected algae, they showed decreased performance in tests of cognitive function, such as recognition memory and sensory-motor gating. Some of these animals developed antibodies against the virus, suggesting that viral replication took place. Furthermore, feeding of chlorovirus to mice was associated with changes in gene expression in the hippocampus, the part of the brain essential for learning, memory, and behavior.

It is not known if the chlorovirus replicates in humans or in mice; only viral nucleic acids were detected. No mention is made of attempts to isolate infectious chloroviruses from humans or mice. The amount of chlorovirus in the oropharynx is not known. However the results of sequence analysis, in which low numbers of sequences were found in each person suggest very low numbers of genomes. Of course, it is possible that virus replication took place some time ago, and its effects linger after replication has subsided.

Chloroviruses are commonly found in inland waters, and the subjects could have acquired the virus via inhalation or drinking contaminated water. It is entirely possible that the virus does not replicate in humans, but is present in the oropharynx as a common environmental contaminant. Many plant and insect virus sequences can be isolated from the human intestinal tract as a consequence of the food we ingest, but there is no evidence that they can replicate at that site. Consequently, chlorovirus might not have any role in the reduced cognitive functions observed in this study. It is possible that exposure to another factor together with chloroviruses, such as heavy metals, is responsible for the observed cognitive differences.

The suggestion that a virus infection might cause subtle cognitive defects is not outlandish. For example, lymphocytic choriomeningitis virus infects rodents congenitally or immediately after birth and establishes a persistent infection of virtually all tissues. These mice show no outward signs of illness, but careful study of infected animals reveals that they are less ‘smart’ than their uninfected peers.

The results are intriguing and warrant more study, including a determination of whether an infectious chlorovirus can be isolated from humans, whether this virus can replicate in human cells in culture, and how they differ from environmental isolates. It would also be important to determine if antibodies to chloroviruses are present in humans, and if they are associated with any diseases. It is too early to conclude that a virus of algae causes altered human neurological functions.