If it looks like a duck and quacks like a duck, so the adage goes, it must be a duck. But if the duck gets infected by a virus so that it no longer looks or quacks like one, is it still a duck? For a team led by researchers from the University of Michigan and The Ohio State University studying how virus infections cause significant metabolic changes in marine microbes, the answer is no. They refer to the infected microbial cells as virocells, a change in name first described in 2011 which reflects the metabolic changes they’ve undergone.

The paper, published in The ISME Journal, won the journal’s 2020 Best Paper Award.

The number of microbes in, on, and around the planet is an astronomical figure, and yet viruses outnumber them. In the ocean, viruses outnumber surface microbes 10 to 1, and 20 to 40 percent of the microbes are infected at any given time. Microbial viruses can thus have significant impacts on the global nutrient cycles regulated by their hosts. For example, microbes that capture and store carbon in the ocean could fix less carbon when infected. Little is known about virus-infected microbial cells that are transformed into virocells, and how the outcomes of these infections can affect the interactions within their ecosystems.

Microbes drive the energy and nutrient cycles that fuel the planet, and viruses control them through infection, but little is known about the impacts of these infections on ecosystem functions. As part of efforts to characterize global microbial diversity with an aim to improve predictive ecosystems models, University of Michigan’s Melissa Duhaime and The Ohio State University’s Matt Sullivan used an experimental approach with a marine phage-host model to study virus-host-nutrient interactions. Their study focused on how virus-infected microbes are transformed into virocells that are metabolically and functionally different from uninfected cells. Duhaime and Sullivan are co-corresponding authors. The study’s lead author is OSU’s Cristina Howard-Varona, a postdoctoral researcher in Sullivan’s lab. Morgan Lindback and Eric Bastien are graduate student coauthors from the U-M Duhaime Lab.

“In this paper, we look at two different viruses infecting the same host (separately) and we compare their metabolic reprogramming,” explained Lindback. “This metabolic reprogramming was quite different. We use the mismatch between the resources the virus needs to make more viruses inside the host as a way of explaining why there is such a difference in virocell metabolic reprogramming between the two phage (a phage is a virus that infects and replicates within bacteria). I was most surprised that Eric was able to find such a good correlation between the resources viruses need and the resources the host has to offer. He found that one virus needed more resources that the host didn't have, and that was the same virus that metabolically reprogrammed the host in surprising ways to gain more resources.” 

Bastien said, “I had the feeling that we always study bacteria in a vacuum, but we need to think about bacteria being infected by viruses all the time. This has huge consequences! Viral infection of bacteria can have ecosystem-level consequences by bursting cells that put nutrients in the environment and infected cells could be taking more nutrients out of the environment to make more viruses. We always need to consider viruses when we think about bacteria.” 

They found that viruses infect their host differently and that the process of infection is what's actually interesting because the virus metabolically reprograms the host in different ways. They hypothesize that this means that different viruses have different impacts on the environment, which is one of their next big questions. 

Next, they asked “what happens to virocell metabolic reprogramming when we change the environment to be more like the ocean where these viruses and host are from? We are about to submit a follow-up paper that looks at the virocell metabolic reprogramming under phosphorus limitation, which is a nutrient that is very limiting in oceans,” added Lindback. Cells in most of the world’s oceans are starved for phosphorus, which limits their growth.

“We found that the virocell metabolic reprogramming was very different under phosphorus limitation and that this had significantly different environmental implications.” 

The bacteria and viruses were isolated from the North Sea and grown up in cultures in the lab where many people worked together to get temporal samples of infection.

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