The availability of next-generation sequencing, and the accompanying capability to process and analyze large amounts of data, has made many previously unthinkable projects possible. Examples include the sequencing of entire microbial genomes to track the spread of antibiotic-resistant infections in a hospital setting, sequencing all the contents of a particular foodstuff to identify meat sources and contaminants, and the microbiome project—a multi-national research effort to characterize the microrganisms colonizing the human body to look for associations with health and disease.
The ability to both get and process data on this large a scale has led to numerous advances in our understanding of the complex relationships between ourselves and our microbial colonizers. Over the last couple of years the microbiome project has generated data suggesting previously unimagined connections between bacteria colonizing our bodies and obesity, cardiac disease, and even personal identification.
As if the complex inter-relationship between bacterial and human cells isn’t enough to grapple with, there is also the virome to consider. As the name suggests, the virome comprises all the viruses in the body, including those that cause acute and chronic infections, those stably integrated within chromosomes, and even phage—the viruses that infect our colonizing bacterial cells. A review published in March in the journal Cell states:
“Studies of the virome are in their infancy because it has only recently become possible to ‘‘see’’ the virome in large sequence data sets using bioinformatic tools that can detect relationships between viruses despite extreme nucleotide sequence diversity”
Unlike the bacterial complement of the microbiome, where conserved sequences (ribosomal 16S RNA) can be targeted and sequenced, analysis of viral DNA and RNA is complicated by the lack of such universal targets. Instead, isolation and sequencing of viral nucleic acid from within a background of mammalian and other microbial DNA relies on shotgun approaches followed by computational analysis to identify viral sequences, or on approaches that require differential isolation of viral particles prior to sequencing.
The Cell review summarizes how, despite being in its infancy, studies of the mammalian virome have already led to the identification of many new viruses of known and unknown function and have also suggested that in some circumstances interactions between viral sequences and host genes may work together to influence disease susceptibility. For example, in mice persistent infection with norovirus and the presence of a specific host allele have been associated with development of inflammatory bowel disease, but the virus or allele alone have no effect. Studies such as these offer hope for a better understanding of diseases that may be viral in origin or have viral components influencing pathogenesis. They also offer the possibility that diseases of currently unknown origin may be attributable to as yet unidentified viral-human interactions.
To me, one surprising thing about the virome is the inclusion of phage–viruses that infect the bacterial cells that inhabit our bodies. (I think my head might explode now). It turns out that even this “virome within the virome”, may have an influence on human health—having a role in regulating the composition of bacterial populations, possibly also interacting directly with the immune system, and perhaps offering us more options for the treatment of bacterial infections.
The ability of phage to regulate bacterial populations is being investigated as a potential alternative to antibiotic treatment. The idea that phage or phage products may have potential as treatment for bacterial infections is not a new idea, phage cocktails having been used as treatment in the pre-antibiotic era. However interest in phage as antibacterial treatments has undergone a recent resurgence due to the ongoing issues with widespread antibiotic resistance and the urgent need to find alternatives to antibiotic treatment. A paper published this week in Antimicrobial Agents Chemotherapy describes the successful use of phage to treat antibiotic-resistant Burkholderia cenocepacia respiratory infections in mice. In that paper, phage delivered via aerosol were effective in clearing antibiotic resistant B. cenocepacia from the lungs of infected mice. Treatment with phage, if successfully translatable into usable therapies, would offer the advantage over antibiotics of very specific targeting of problem bacterial species because phage have a specific and narrow host range.
Both of these papers illustrate how studies on the virome—both of mammalian and bacterial cells—are contributing insights to the complexity of the relationships between organisms living in human hosts, and also show how ideas gained from understanding these relationships can potentially be applied to the treatment of disease.
Here are the Papers:
Virgin, H. (2014). The Virome in Mammalian Physiology and Disease Cell, 157 (1), 142-150 DOI: 10.1016/j.cell.2014.02.032
Semler, D., Goudie, A., Finlay, W., & Dennis, J. (2014). Aerosol phage therapy efficacy in Burkholderia cepacia complex respiratory infections. Antimicrobial Agents and Chemotherapy DOI: 10.1128/AAC.02388-13
More Information about the Virome:
Williams, C.P. (2013) The Other Microbiome. PNAS 110, 2682-2684. www.pnas.org/cgi/doi/10.1073/pnas.1300923110