Giant mimivirus does its replication in-house

THE world's largest known virus just got bigger, and analysis of its genome supports the controversial idea that giant viruses shaped the cells of all animals and plants. Armed with almost 1000 genes, the mimivirus is a monster compared with classic viruses such as HIV or the flu virus, which seldom have more than 10 genes. Jean-Michel Claverie of the Structural and Genomic Information Laboratory in Marseilles, France, has performed the first analysis of its genetic machinery, identifying which of the mimivirus's genes are switched on during each stage of infection.

He found that the virus has 75 more genes than previously thought. Crucially, Claverie's study reveals that the mimivirus uses its own genes and proteins to orchestrate its replication (Genome Research, DOI: 10.1101/gr.102582.109).

Classic viruses insert their DNA into the nuclear DNA of the cells they infect and let their host do the hard work of replication for them (see diagram). In contrast, the mimivirus constructs a massive "factory" within the cell, where millions of new viruses, or virions, are produced. These eventually burst out from the dead host cell to spread and infect other cells. The only other viruses that replicate outside the nucleus are poxviruses, but even they rely on the nucleus to replicate some of their DNA.

In order to create the virus factory, the mimivirus appears to steal some of the host cell's resources. Claverie found that the virus has a gene that codes for a protein which carries ATP - the molecule that stores energy in a form that cells can use. It is also equipped to scavenge amino acids - the building blocks of proteins - from its host, thanks to genes that make proteins which transport amino acids.

Claverie found that these genes are activated when the mimivirus first invades a cell. He believes they are used to set up the virion factory, which then allows the mimivirus to replicate without help from the host cell's own nucleus. In fact, the factory is so large it was originally mistaken for a nucleus.

Claverie says the mimivirus's independence supports the theory that giant viruses gave rise to the nuclei that package up DNA in all plant and animal cells. Philip Bell of Macquarie University in Sydney, Australia, who first put forward the theory, agrees. "This paper shows the ability of viruses to completely take over cells," he says. "This is one of the key aspects of my theory."

Abraham Minsky of the Weizmann Institute in Rehovot, Israel, says the results support his own team's recent study showing that the mimivirus lives in a cell's cytoplasm entirely independently of the host nucleus.

But David Moreira of the University of Paris-South, France, remains unconvinced. He argues that the mimivirus owes its enormous size to its ability to "pickpocket" genes from the eukaryotic cells it infects. "This paper does not alter my view," he says.