Biggest Virus Ever Discovered Yields First Virophage

Even more remarkable than Bernard La Scola and colleagues' recent identification of a mammoth mimivirus, was the unexpected discovery that this newly-isolated giant virus was itself infected with a tiny icosahedral virus The researchers, who published their findings online in Nature this August (<doi:10.1038/nature07218>), named the new strain of Acanthamoeba polyphaga mimivirus (APMV) "mamavirus" and its 50 nm viral parasite "Sputnik," after "traveling companion" in Russian.

Whereas the main features of mamavirus closely resemble those seen in other mimivirus, including formation of complex virus-producing factories and typical particle morphology with a fibril-covered multi-layered membrane, Sputnik is an entirely new find. Its genes appear evolutionarily derived from 1) a currently unknown family of small viruses, 2) an archaeal virus (or plasmid), and 3) a mimivirus/mamavirus. "One of Sputnik's most remarkable characteristics is its apparent chimeric origin" which, says La Scola a principal investigator at the Université of Mediterranée in Marseille, "seems to be one of the most convincing cases so far for gene mixing and matching within the virus world."

The research team initially spotted the smaller viruses reproducing inside mamaviral giant factories, high jacking its host-acquired ATP to form their own virions. Transmission electron microscopy revealed that mamavirus and Sputnik particles were generated simultaneously but at different locations and with different kinetics. Importantly, Sputnik reproduction was deleterious to the APMV, resulting in deformed mamavirus progeny. In most cases, several capsid layers accumulated asymmetrically at only one pole of the mamavirus particles and fibril distribution was erratic. When the researchers co-inoculated mamavirus and Sputnik into amoebas, there was a roughly 70% decrease in infective mamavirus particles. Infection with Sputniks, it seems, had sickened the mamavirus.

"The finding that Sputnik can pirate the factory of another virus to propagate at the expense of its host makes it a 'virophage,' an infecting agent functionally analogous to bacteriophage," says La Scola who urges a search for additional virophages "to shed more light on the unique modes of viral interactions. It is probable, for example, that virophage serve as vehicles for lateral gene transfer between giant viruses, which we now know, constitute a quantitatively important and ubiquitous part of the large eukaryotic DNA virus population in diverse marine environments. "Indeed, the presence of three APMV genes in Sputnik suggest that gene transfer between a virophage a giant virus is not only possible, it's probably central to viral evolution," he says.

Jean-Michael Claverie, co-discoverer of the first mimivirus and director of the Mediterranean Institute of Microbiology, considers the discovery of Sputnik a pivotal one and says "the fact that a virus can get sick makes it more alive." According to Claverie, "discovery of a virophage infecting a mamavirus factory lends credence to the radical new view known as 'Girus,' which defines the factory, not the infecting particle, as the actual viral organism. Claverie sees no difference between the cell-like virus factory and intracellular bacteria such as Rickettsia and Chlamydia, rendering viruses as bone fide "living" microorganisms.

Marcia Stone is a science writer based in New York City. More of her work can be seen on www.mstoneworks.net