Wait…viruses are alive?!

It’s one of those basic tenets of biology even high schoolers learn about: Viruses, while widespread and deadly, are not alive, which is why we have such a hard time getting rid of them.

Unfortunately, it now appears that another basic tenet has bit the dust, because with the addition of a new study published in Scientific Advances, the evidence seems to be pointing to viruses actually being alive.

Let’s review: For a long while, viruses have generally been seen as non-living organisms. It has been argued that they are merely pieces of DNA and RNA shed by living cells—a point strengthened by the fact that viruses must invade a living cell and hijack the cell’s machinery in order to reproduce.

There’s some new theories in town

“Many organisms require other organisms to live, including bacteria that live inside cells, and fungi that engage in obligate parasitic relationships — they rely on their hosts to complete their lifecycle,” said co-author Arshan Nasir, a graduate student at the University of Illinois at Urbana-Champaign. “And this is what viruses do.”

Beyond how they reproduce, it was hard to tell whether viruses are the detritus of living cells, or whether they derived through a different means. Viruses are pretty difficult to classify as compared to other organisms. One of the biggest problems in regard to viruses is the sheer number of them, as it is estimated that over 1,000,000 virus species exist, although we have only managed to identify and sequence about 4,900. And because viruses tend to mutate very quickly, their genetic material is hard to track, especially in terms of deep evolutionary signals.

Going back to the basics

The researchers therefore took a different view of viral history. Instead of focusing on the genetic sequences contained within viruses, they chose to focus on their shapes—specifically, the way their proteins fold into 3D structures.

Protein folds don’t tend to change anywhere near as often as genetic information does, making folds a better marker of ancient events. So, by comparing proteins fold structures across various branches of the tree of life, the researchers believed it would be easier to reconstruct the evolutionary history of the folds and thus the history of viruses.

The researchers analyzed all of the known protein folds in 5,080 organisms that represented every branch of the tree of life—including 3,460 viruses. After analyzing the folds, they determined that 442 protein folds are shared between viruses and cells, while 66 are unique to viruses alone.

“This tells you that you can build a tree of life, because you’ve found a multitude of features in viruses that have all the properties that cells have,” Caetano-Anollés said. “Viruses also have unique components besides the components that are shared with cells.”

Moreover, the team discovered genetic sequences in viruses that are unlike anything seen in cells, contradicting the idea that viruses derived their genetic information purely from cells.

With this data, the researchers used computational methods to build trees of life with viruses included. The end result suggests “that viruses originated from multiple ancient cells … and co-existed with the ancestors of modern cells,” the researchers wrote.

It also appears that the proteins coats that protect viruses when they move outside of cells emerged not long after modern cellular life did, as the protein coats (known as capsids) contain many of the unique protein folds.

“This is no more,” said co-author Gustavo Caetano-Anollés, a University of Illinois crop sciences and Carl R. Woese Institute for Genomic Biology professor. “Viruses now merit a place in the tree of life. Obviously, there is much more to viruses than we once thought.”

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Feature Image: Julie McMahon