Giant viruses may be more alive than we thought

Viruses rely on the machinery of their host cells to produce proteins, but some giant viruses encode a key part of this toolkit in their genome, allowing them to direct the host cell to produce more of its own proteins. The discovery adds to the sense that giant viruses are blurring the line between living and non-living things.

Giant viruses have attracted increasing attention from biologists since 2003, when a mysterious microbe found in Bradford, UK, was first identified as a “mimivirus” that infects amoebas. Some are larger than typical bacteria, have complex shapes and have hundreds of genes.

Some of these genes encode components of the translation machinery, the step that turns genetic information into proteins. In cells, translation is carried out by structures called ribosomes and is initiated by molecular assemblies called initiation complexes.

To see if giant viruses have a comparable system, Max Fels at Harvard Medical School and his colleagues investigated what happens inside infected amoebae and how the mimivirus manipulates the host once infection has begun.

The team isolated ribosomes from infected cells and identified the viral proteins associated with them. “That was the first hint that these might be the factors we were looking for,” says Fels.

They then knocked out the genes encoding the viral complex by replacing them with altered DNA sequences so that the virus could no longer produce the corresponding proteins. This caused virus production to drop as much as 100,000 times and the formation of new infectious particles was drastically impaired.

Together, the findings suggest that the viral complex redirects the host’s protein synthesis machinery during infection and ensures that viral structural proteins are produced in large quantities. Experiments suggest that they can do this even under harsh conditions, such as nutrient deprivation and oxidative stress, which typically reduce protein synthesis in host cells.

This discovery raises a deeper evolutionary question: how did these viruses acquire this ability? Some scientists think that giant viruses are the descendants of extinct cellular life forms, but others think that they arose as normal viruses that stole genes from their hosts.

“Giant viruses acquired a wide range of cellular machinery from their eukaryotic hosts during their evolution,” he says. Frank Aylward at Virginia Tech, who was not involved in the study. During infection, gene exchange can occur, and over long evolutionary time periods, natural selection can preserve genes that confer an advantage.

Many of the largest viruses harbor single-celled organisms such as amoebae and their environments, which can fluctuate more than the relatively stable tissues of multicellular hosts. Therefore, maintaining flexible control over protein synthesis could offer a selective advantage, Aylward says.

The work also leaves key questions unresolved. The mimivirus genome encodes around 1000 proteins, but the functions of most are still unknown. For example, it is not yet clear how exactly these viruses regulate protein production during a single infection cycle.

“Viruses have long been considered more passive entities in the evolution of living systems,” he says Hiroyuki Ogata at Kyoto University in Japan. “This study shows that giant viruses can reshape molecular systems that are otherwise stably conserved in domains of life.”

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