Illustration of a mimivirus, a kind of giant virus that infects amoebae
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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 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”, which infects amoebae. Some are larger than typical bacteria, display intricate shapes and have hundreds of genes.
Some of these genes code for 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 initiated by molecular assemblies called initiation complexes.
To find out whether giant viruses have a comparable system, Max Fels of Harvard Medical School and his colleagues investigated what happens inside infected amoebae and how the mimivirus manipulates the host machinery once the infection begins.
The team isolated ribosomes from infected cells and identified viral proteins associated with them. “That was the first hint that they might be the factors we were looking for,” says Fels.
They then knocked out the genes that code for the virus 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 by up to 100,000 times, and the formation of new infectious particles was drastically weakened.
Together, the findings suggest that the viral complex intervenes to redirect the host’s protein synthesis machinery during infection, ensuring that viral structural proteins are produced in large quantities. The experiments suggest that they can do this even under harsh conditions, such as nutrient deprivation and oxidative stress, which usually reduce protein synthesis in the host cells.
The discovery raises a deeper evolutionary question: how did these viruses acquire such an ability? Some scientists believe giant viruses originated from extinct cellular life forms, but others believe 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 of Virginia Tech, who was not involved in the study. Gene exchange can occur during infection, and over long evolutionary time scales, natural selection can retain genes that confer an advantage.
Many of the largest viruses hijack unicellular organisms such as amoebae, and the environment within them can fluctuate more than the relatively stable tissues of multicellular hosts. Therefore, retaining flexible control over protein synthesis may offer a selective advantage, says Aylward.
The work also leaves key questions unsettled. The mimivirus genome codes for around 1,000 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 rather passive entities in the evolution of living systems,” says Hiroyuki Ogata of Kyoto University in Japan. “This study shows that giant viruses can reshape molecular systems that are otherwise stably conserved across the domains of life.”
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