Of all the Earth’s biomes, the ocean has emerged as the source for major discoveries on the interaction of viruses with their microbial hosts. 1,2,3 Ocean viruses were the inspiration for early hypotheses of the so-called “viral shunt,” by which viral killing of microbial hosts redirects carbon and nutrients away from larger organisms and back...

There are an estimated 10 31 viruses on Earth. That is to say: there may be a hundred million times more viruses on Earth than there are stars in the universe. The majority of these viruses infect microbes, including bacteria, archaea, and microeukaryotes, all of which are vital players in the global fixation and cycling of key elements such as carbon, nitrogen, and phosphorus. These two facts combined—the sheer number of viruses and their intimate relationship with microbial life—suggest that viruses, too, play a critical role in the planet’s biosphere.

Among these discoveries are “giant” marine viruses, with capsid cross-sections that can exceed 500 nm, an order of magnitude larger than prototypical viruses. Giant viruses infect eukaryotic hosts, including the protist Cafeteria and unicellular green algae.6,7 These viruses also carry genomes larger than nearly all previously identified viral types, in some cases upwards of 1 million base pairs. In both marine and nonmarine contexts, researchers have even identified viruses that can infect giant viruses, the so-called virophages,8 a modern biological example of Jonathan Swift’s 17th-century aphorism: “a flea/ Hath smaller fleas that on him prey;/ And these have smaller fleas to bite ’em;/ And so proceed ad infinitum.”

It is apparent that we still have much to learn about the rich and dynamic world of ocean microbes and viruses. For example, a liter of seawater collected in marine surface waters typically contains at least 10 billion microbes and 100 billion viruses—the vast majority of which remain unidentified and uncharacterized. Thankfully, there are an increasing number of high-throughput tools that facilitate the study of bacteriophages and other microbe-infecting viruses that cannot yet be cultured in the laboratory. Indeed, studying viruses in natural environments has recently gone mainstream with the advent of viral metagenomics, pioneered by Forest Rohwer and colleagues at San Diego State University in California.9

More recently, culture-free methods have enabled insights into questions beyond that of characterizing viral diversity. For example, Matthew Sullivan’s group at the University of Arizona and colleagues recently developed an adapted “viral tagging” method, by which researchers can now characterize the genotypes of environmental viruses that infect a host of interest, even if those viruses cannot be isolated in culture.10 These and other techniques—and the increasingly interdisciplinary study of environmental viruses—bring the scientific community ever closer to a clearer understanding of how viruses shape ocean ecology.

Not so picky

© SCIEPRO/SCIENCE SOURCEResearchers have long believed viruses to be extremely host-specific, meaning they should infect a taxonomically narrow subset of the microbial community at a given time in any given environment. But recent evidence suggests that marine viruses may not be so picky after all, and may be capable of infecting multiple microbial species or even more distantly related organisms. For example, a 2003 study demonstrated that certain cyanophage genotypes can infect not only different strains within the same cyanobacteria species, but different cyanobacterial genera as well.11 And a 2011 analysis of more than 20 years of viral-host infection assays revealed that naturally occurring viruses from a diversity of taxa range from specialists to generalists.12 Hence, viruses are certainly not limited to a single host genotype, nor to a particular species, and perhaps not even to a genus!

Ostensibly, viruses should decrease the oceanic abundance of the targeted microbial lineage. Quantitative estimates of virus-mediated killing demonstrate that viruses are, in some cases, as important as grazers, such as protists and zooplankton, in selectively killing microbes. Such a relationship might, as a consequence, lead to dynamic fluctuations in viral and microbial populations, as viruses deplete susceptible bacteria. Indeed, new viral subtypes arise frequently and rapidly, and previously rare subtypes can quickly increase in abundance.

The sheer number

of viruses and their intimate relationship with microbial

life suggest that viruses

play a critical role

in the planet’s biosphere.

Nonetheless, direct evidence for coupled oscillations in virus-microbe systems in the oceans is limited. It’s even possible that viruses do not play a strong role in controlling a microbe’s population. Or, in some instances, marine viruses that actively infect and lyse microbes may simply not have been accounted for in prior surveys. For example, until recently, the most abundant marine bacterial lineage, SAR11—estimated to make up a third of all prokaryotic cells in surface waters—had no documented viruses that were known to infect it, leading to speculations that SAR11’s observed high abundance was due, in part, to its lack of a phage predator. However, scientists recently discovered a group of non-tailed podoviruses that can and do kill SAR11. These viruses, previously unknown to science, are now estimated to be the most abundant viral type in the oceans and could be an important factor in driving changes in SAR11 populations.13

Where do all the nutrients go?

© THOM GRAVESThe death of a host cell and the release of viral progeny are but one part of the story of how viruses affect the ocean ecosystem. Lysis of microbes also releases carbon and other organic nutrients, previously tied up as cellular materials, back into the environment. Marine microbes can assimilate these organic materials, leading to a paradoxical consequence of viral infection: the death of one host may indirectly benefit other microbes.

This hypothesis, which we term “viral priming,” has been documented in experimental model systems using microbes that predominantly occur near the ocean surface. In one illustrative example, viral lysis of a bacterium infected in the lab released organic-iron complexes that were rapidly taken up by other marine bacteria, as well as by diatoms (unicellular eukaryotic algae).14 This assimilation increased growth rates of the nontargeted organisms. In a second example, the removal from an experimental system of viruses that infect and lyse heterotrophs slowed Synechococcus cell growth and proliferation, presumably due to a decrease in virus-mediated nutrient release.15 Thus, what is bad for one microbial cell may indeed be good for others. In the deep ocean, however, we still do not yet know what happens to virus-released organic matter. Is it assimilated, buried, or otherwise exported? What happens to organic matter miles below the surface is important because it closes the loop of the global carbon cycle. Free carbon in the deep ocean is “ancient” (4,000–6,000 years old) and largely recalcitrant to assimilation by microbes, suggesting there may be another supply of this material. Viral lysing of deep-ocean microbes may be a potential source.16

Furthermore, even before lysis, the infection of microbes alters host metabolism. Virus-induced changes in host metabolism can be so significant that the resulting infected particle is, biochemically and metabolically, a very different cell. For example, phage-infected cyanobacteria exhibit a higher rate of photosynthesis than their noninfected counterparts, presumably changing their rate of fixation of carbon from the environment until they are eventually killed by the infection. Bacterial cells undergoing active phage infections can also have altered distributions of other major elements, such as nitrogen and phosphorus, making them biochemically unique.

Moreover, viruses can establish persistent infections within their microbial host cells—similar to infections established by viruses within large eukaryotic hosts, as occurs in the case of retroviral infections—by integrating their genomic material into that of their host, forming what is called a “lysogen.” (See diagram above.) The fate of infected cells may itself be coupled with the availability of carbon and nutrients in the environment. A recent study found that marine phages were more likely to initiate lysogeny, instead of lysis, when their hosts were nutrient-depleted.17 Hence, viruses that may “want” to lyse their hosts may not be able to—or, perhaps, they have evolved to respond to host physiology so as to kill their hosts only when it is more likely that other healthy hosts will be available to infect, which may be indicated by the physiological status of their current host. However, lysogeny is often harder to detect than lysis because the viruses are largely “hidden” within the host. In future, our understanding of viral-host interactions will need to take into account not just who infects whom, but what happens after that.

Viruses, in theory

© ALEXIS ROSENFELD/SCIENCE SOURCEGiven the difficulties in quantifying the role viruses play in complex environments, researchers have turned to mathematical models to help shed light on what viruses might be doing to their hosts and the consequences of such interactions for the ocean system. Like many mathematical models in biology, these models can be very useful in making qualitative and quantitative predictions and in making sense of complex processes. But they also make simplifying assumptions. So, what do these models assume, what have they helped discover, and how can they help shape what we know about viral interactions with their hosts? Answering these questions requires an illustrative example. Here, we briefly discuss models that examine changes in the population densities of hosts and viruses in a community.

Consider the question: How does the population size of a particular bacterial lineage depend on interactions with a particular set of viruses? Mathematical models deconstruct interactions between hosts and their environment, between viruses and hosts, and between viruses and the environment. For example, the infection of a marine cyanobacterium by a cyanophage can lead to lysis in approximately 12 hours. The net effect is the death of a host cell, the release of ~50 progeny viruses, and the release of organic material from the original cell as both virus particles and cellular debris. Hence, a model may ignore the complicated intracellular dynamics and focus on the output, breaking down the entire process in terms of a representative “chemical” reaction, such as 1 Host + 1 Virus = 50 Viruses. Then, the population dynamics of hosts and viruses can be derived from these reactions just as one would derive chemical reaction kinetics.

The art of modeling is to decide when and where details matter. The details, however, depend on the question. Hence, efforts to characterize intracellular dynamics of infected cells require consideration of gene-gene interactions, and particularly the interaction of viral gene products with host physiology. Likewise, efforts to characterize extracellular dynamics require understanding of the rate at which hosts and viruses interact, particularly in complex environments.

Perhaps the most exciting innovation in the area of virus-host modeling is the study of coevolutionary dynamics. Unlike in most models of chemical kinetics, the components (hosts and viruses) evolve over time. Coevolutionary models are technically challenging, given that the genotypes in the community (and in the model) must keep changing. Nonetheless, such models have been used to generate key hypotheses regarding the long-term dynamics of diverse microbial and viral populations. For example, an evolutionary kill-the-winner model was used to suggest that viral and bacterial strains may change rapidly even as total population size and total diversity remain relatively constant.18 Similarly, coevolutionary models have suggested that long-term coexistence of diverse microbial and viral communities should be expected, so long as there are trade-offs between infection and other host physiological rates, such as growth rate or nutrient uptake rate.19

The challenge is to reconcile model predictions with biological reality. For example, Debbie Lindell’s group at Technion–Israel Institute of Technology recently discovered a novel trade-off in which hosts that evolve resistance to certain viral infections may be increasingly susceptible to infection by other viral types with which they have not coevolved.20 This type of discovery further supports the need for considering viral-host interactions in a dynamic community context.

It’s a microbial and viral world

The potential role of viruses in marine biogeochemical cycles has been discussed for nearly 2 decades now, yet the quantitative influence that viruses have at regional and global scales remains largely unresolved. Fortunately, there is a growing interest in the ecological role of ocean viruses. Indeed, as marine microbiologist Mya Breitbart of the University of South Florida posed it, the science of environmental viruses is entering into an exciting period of “truth or dare.”3 That is to say, there are many established tenets of viral-host interactions in the oceans that are oft-repeated, but that are just now being put to the test. There are also many tenets that researchers should be “dared” to prove, or at least further substantiate. Indeed, a working group that we organized to study ocean viral dynamics at the University of Tennessee’s National Institute for Mathematical and Biological Synthesis is but one example of collaborations amongst experimentalists and modelers to characterize viral-host interactions and their consequences on a global scale. If the working group is any guide, future work on ocean viruses will include efforts to combine virus-driven biogeochemical processes, molecular biological data, and mathematical models in a unified context.

Ocean viruses may turn over as much as 150 gigatons of carbon per year—more than 30 times the standing abundance of carbon in marine plankton.

A better quantitative assessment of the role of viruses in the ocean will have important implications for understanding past trends in, and future changes to, the Earth system. Curtis Suttle of the University of British Columbia has estimated that ocean viruses may turn over as much as 150 gigatons of carbon per year1—more than 30 times the standing abundance of carbon in marine plankton. This recycling of carbon and other nutrients suggests that viruses need to be considered in quantitative, dynamic models of global change.

Global-change models integrate geophysical processes with the biology of microbes and metazoans to predict the dynamics of carbon nutrients and biodiversity. However, the smallest yet most abundant biotic agents on the planet—viruses—are rarely, if ever, included in such models. As the Intergovernmental Panel on Climate Change noted in a 2007 report (our emphasis): “The overall reaction of marine biological carbon cycling (including processes such as nutrient cycling as well as ecosystem changes including the role of bacteria and viruses) to a warm and high-CO 2 world is not yet well understood. Several small feedback mechanisms may add up to a significant one.”



Joshua S. Weitz is an associate professor in the School of Biology at the Georgia Institute of Technology in Atlanta. Steven W. Wilhelm is a professor in the Department of Microbiology at the University of Tennessee-Knoxville.

This article is adapted from a review in F1000 Biology Reports, DOI:10.3410/B4-17 (open access).