Study documents mechanism by which viruses hijack host machinery

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Viruses compartmentalize bacterial hosts to hijack their cellular machinery

The beginning of 2017 is proving to be pivotal for virology research considering two breakthrough studies have already been reported within the first month. One report, published last week in Nature, showed how one class of virus uses a trick to override natural signals that would otherwise stop them from replicating. The other goes on to explain that viruses can communicate amongst themselves to coordinate infection to help the descendants to decide how to proceed with the process of infection. Both these phenomenon were previously unheard of for viruses.

In another paper published in Science on January 13, a group of researchers from University of California, San Diego reported some interesting observations. These researchers conducted a series of experiments that allowed them to visually document in detail what happens inside bacterial cells as the invading viruses, also called bacteriophages, replicate.

They saw that large viruses reprogram the cellular machinery of bacteria during infection to more closely resemble an animal or human cell. This process allows these phages to trick cells into producing hundreds of new viruses, which eventually explode from and kill the cells they infect.

“Scientists have been studying viruses for a hundred years, but we’ve never seen anything like this before,” said Joe Pogliano, a professor of molecular biology who headed the research team. “Every experiment produced something new and exciting about this system.”

How viruses takeover the host machinery?

Upon infection, the bacteriophages destroy the existing architecture of their host cells and hijack the cellular machinery. This is followed by manipulation of the entire cell into an efficient, centralized factory to produce the next generation of viruses. This process is well known. However, Pogliano and his colleagues observed that ‘this factory and the surrounding arrangement of the infected cell are remarkably similar to the organization seen in plant and animal cells.’

Cryo-electron tomography image showing the reorganization of the bacterial cell by viral infection. Now, it resembles a more complicated plant or animal-like cell with a blue nucleus-like compartment and ribosomes, the smaller yellow structures. The reproducing viruses appear with light green heads and blue-green tails. Image Courtesy : The Villa lab
Cryo-electron tomography image showing the reorganization of the bacterial cell by viral infection. Now, it resembles a more complicated plant or animal-like cell with a blue nucleus-like compartment and ribosomes, the smaller yellow structures. The reproducing viruses appear with light green heads and blue-green tails. Image Courtesy : The Villa lab

Plant and animal cells, generically called ‘eukaryotic cells’, contain specialized compartments which separate cellular processes. Bacteria lack such compartmentalization in structure or in function. For example, bacteria do not contain an enclosed nucleus – the storehouse of genetic information in the cell.

Strikingly, Vorrapon Chaikeeratisak, a postdoctoral fellow, and Katrina Nguyen, a graduate student in Pogliano’s laboratory, found that invading viruses re-organize the structures within bacteria. They build compartments to segregate the different processes going on during infection, to mimic those found in eukaryotic cells.

“These compartments enclose the entire viral DNA, just as a nucleus does in a plant or mammalian cell,” said Chaikeeratisak, the first author of the paper. “DNA processes, like replication or transcription, occur inside the compartment while proteins are produced outside the compartment.”

Chaikeeratisak and Nguyen acquired these images at extremely high magnification using a specialized technique called ‘cryo-electron tomography’ and were helped in this venture by Elizabeth Villa, a professor of chemistry and biochemistry at UC San Diego, and David Agard, a professor of biochemistry and biophysics at UC San Francisco.

Their pictures revealed that that the phage assembled a nucleus-like compartment when it infected a bacterial cell. The phage genome was completely enclosed by an apparently contiguous protein shell, within which DNA replication, recombination, and transcription occurred.

Viral progeny assembled on the membrane of the host, but later moved to the surface of the compartment for DNA packaging. Ultimately, viral particles were released from the compartment and the cell burst open so that the new viruses can spread out to infect new cells. These results demonstrate that phages have evolved a specialized structure to compartmentalize viral replication.

Compartmentalisation ensures DNA replication and transcription inside the nucleus and protein synthesis and metabolic processes outside it. Image Courtesy : Vorrapon Chaikeeratisak, Kanika Khanna, Axel Brilot, Katrina Nguyen
Compartmentalisation ensures DNA replication and transcription inside the nucleus and protein synthesis and metabolic processes outside it. Image Courtesy : Vorrapon Chaikeeratisak, Kanika Khanna, Axel Brilot, Katrina Nguyen

“These observations of viral manipulation of a cell are completely unexpected, as no bacterial virus has been seen to reorganize a cell in so drastic a manner,” said Pogliano. “The restructuring of a simple cell to resemble an existing, more complicated system blurs the line between simple bacterial cells and those of ‘higher’ organisms, such as plants and animals.”

Missing link in evolution?

This study reignites the ever-lasting debate regarding the evolution of multi-celled organisms. One such hypothesis called ‘viral eukaryogenesis’ attempts to explain how the gulf between prokaryotic and eukaryotic cellular design arose. According to this hypothesis, first proposed by Phillip Bell in 2001, the first eukaryotic cell was a multimember consortium consisting of a viral ancestor of the nucleus, an archaeal ancestor of the eukaryotic cytoplasm, and a bacterial ancestor of the mitochondria.

“It may be too early to know if this particular virus is an intermediate step in the transition from bacteria and viruses to multicellular eukaryotes, but this discovery could broaden knowledge about the origins of life as we know it,” said Pogliano.