In brief (August 2013, part I) – prions and giant viruses

Picks for this month, first part:
prions, alcohol and yeast, or how an environmentally responsive prion protein may help yeast to cope with high concentrations of ethanol,
giant viruses, or how the discovery of viruses larger in size and DNA content than any virus known so far challenges the way scientists think of viruses.

  • Prions, alcohol and yeast

Prions are most commonly associated with “mad cow disease” and Creutzfeldt-Jakob disease. From our human point of view, they are nasty little things. However, they may prove beneficial for other organisms. In a study published in Cell, Holmes et al. report that the yeast Saccharomyces cerevisiae seems to make use of the prion form of a protein called Mot3 to cope with changes in its environment.

Prions are essentially misfolded forms of normal proteins and may thus be associated with a gain or a loss of function for these proteins. In normal growth conditions in the lab, the transformation of Mot3 into its prion form [MOT3+] in yeast happens spontaneously, albeit very rarely. The researchers observed that when yeast cells were exposed to high concentrations of ethanol (alcohol) similar to those naturally occurring during the fermentation process the amount of the prion form [MOT3+] present in the cells was increased by a factor 10. In parallel, the yeast cells, which usually live as single isolated cells, reorganized into a multicellular state, remaining “stuck” to one another after multiplication. When the yeast cells were subsequently exposed to low levels of oxygen (which also happens in the fermentation process), they reverted back to harboring mostly normal forms of Mot3 and returned to a unicellular state.

The authors of the study hypothesize that the conversion of Mot3 between its normal and its prion forms acts as a molecular switch responding to environmental conditions and allowing cells to shift between unicellular and multicellular living states via the regulation of another factor called FLO11 known to be important in cell-cell adhesion.

(Holmes et al., Cell 28 March 2013, doi: 10.1016/j.cell.2013.02.026)

  • Giant viruses

Viruses have long been considered tiny non-living things, mere small packages of genetic material unable to replicate by themselves. Most viruses do not contain more than ten genes and are some 15-20 times smaller in size than an E. coli bacterium. About ten years ago, the discovery of a giant virus by a French research team came to challenge this view of things. Dubbed Mimivirus (for microbe-mimicking virus), it was larger in size and DNA content than even some bacteria, but replicated by infecting amoebae (single-cell eukaryotic organisms) and using its host cellular machinery, like a typical virus. The same research team has now come up with an even bigger virus, in fact one that harbors the largest genome ever seen in a virus.

In July, Philippe et al. reported in Science the discovery of two giant viruses which they called Pandoraviruses. One was found in a sample collected from a marine sediment layer off the coast of Chile (P. salinus) and the other in a mud sample from a shallow freshwater pond in Australia (P. dulcis). Despite their large bacteria-like size, they proved to be viral in nature. They lacked the traditional hallmarks of cellular organisms (e.g. they could not make their own proteins, they did not produce energy via ATP, they did not replicate by dividing into two daughter cells) and their replication cycle, which the researchers observed in its entirety (10-15h) using light and electron microscopy, proved virus-like: after being taken up by the amoeba, the viral particles emptied their protein and DNA content into the host cell and made use of the host cellular machinery to replicate, eventually leading to the host cell splitting open and the release of hundreds of new viral particles. Sequencing of the genome of these purified particles revealed a genome size of 2.5 million DNA bases for P. salinus, making it the largest viral genome known so far. Interestingly, the researchers found that only about 7% of P. salinus 2,556 putative genes matched DNA sequences recorded in existing databases.

The discovery of Pandoraviruses, with their large genomes rivaling those of bacteria and even edging into the eukaryotic realm, certainly challenges the way scientists may think of viruses. In addition, the fact that most of the pandoravirus’s DNA sequences resemble nothing known is a reminder of how little we know about Earth’s microbial diversity and how much there is still to learn about viruses and their relationships with cellular organisms.

(Philippe et al., Science 19 July 2013, doi: 10.1126/science.1239181)

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