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, enabling them to direct the host cell to produce more of their own proteins. The discovery adds to the sense that giant viruses blur the boundary between living and non-living things.

Giant viruses have drawn growing attention from biologists since 2003, when a mystery microbe found in Bradford, UK, was first identified as a “mimivirus”, which infects amoebae. Some are larger than typical bacteria, display intricate shapes and have hundreds of genes.

Some of these genes encode components of the machinery for translation, 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 determine whether giant viruses possess a comparable system, Max Fels at Harvard Medical School and his colleagues examined what happens inside infected amoebae and how the mimivirus manipulates the host machinery once infection begins.

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

Then they knocked out the genes encoding the viral complex by replacing them with altered DNA sequences so the virus could no longer produce the corresponding proteins. This caused viral production to drop by up to 100,000-fold, and the formation of new infectious particles was drastically impaired.

Together, the findings suggest that the viral complex steps in to redirect the host’s protein-synthesis machinery during infection, ensuring that viral structural proteins are produced in large amounts. The experiments suggest they can do this even under harsh conditions, such as nutrient deprivation and oxidative stress, which typically reduce protein synthesis in host cells.

The discovery raises a deeper evolutionary question: how did these viruses acquire such a capability? Some researchers think giant viruses are descended from vanished cellular life forms, but others think they originated as normal viruses that stole genes from their hosts.

“Giant viruses have acquired a wide range of cellular machinery from their eukaryotic hosts throughout their evolution,” says Frank Aylward at Virginia Tech, who wasn’t involved in the study. Gene exchange can occur during infection, and over long evolutionary timescales, natural selection may retain genes that confer an advantage.

Many of the largest viruses hijack single-celled organisms such as amoebae, and the environment within them that may fluctuate more than the relatively stable tissues of multicellular hosts. Therefore, retaining flexible control over protein synthesis could offer a selective advantage, says Aylward.

The work also leaves key questions unresolved. The mimivirus genome encodes around 1000 proteins, yet the functions of most are still unknown. For example, it isn’t yet clear how precisely these viruses regulate protein production over the course of a single infection cycle.

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