When you have to make a tough decision, a difficult choice, one that will affect your life and the lives of those around you, you always have to involve them in the process, and you will find that the wisest thing to do is to unite and make the decision collectively…

Starting from us, humans, and reaching bacteria, collective decision making can be a matter of life and death, yet many factors can influence the way we think and switch our behavior from one way to another. In quorum sensing, bacteria behave in a completely different way upon reaching a certain population density, from the way each one would behave individually.

This is all obvious, but I was lately wondering, do viruses exhibit any form of such “attitude”?? What is the equivalent to quorum sensing in the world of viruses?

The work in this field was all focused on bacterial viruses or bacteriophages, and especially on the temperate lambda virus (a phage that infects E. coli).Temperate means that upon infecting a bacterial cell, the virus will be allowed to choose between two scenarios:

Either: the lytic pathway, in which the virus will use the bacterial resources to replicate itself several times, then bursting out of the cell, killing it and releasing the viral progeny.

Or: the latency or lysogenic pathway, in which the virus integrates its genetic material into that of the host, undergoing minimal transcription and translation, and just replicating and vertically transferring it as the cell divides.

So what really helps or even forces the virus into a certain direction? For a long time, it was thought that the choice is completely random, and greatly affected by environmental conditions. But Joshua Weitz (assistant professor in the school of biology, Georgia Tech) and his team were not satisfied by this answer. They wanted to justify the experimental observation that when one virus infects the cell, the result would be lysis and cell death, whereas if two or more co-infect the host, the result would be latency.

Their mathematical model, based on the gene regulatory dynamics of the λ phage, shows us that the true answer lies in the levels of “gene expression”. Apparently, the process turned out to be controlled by three key genes: cro, cI, and cII. These genes are bound together by a decision loop (a feedback system) that is nonlinear and thus is tremendously affected by minimal changes in the levels of their expression into proteins, which depends on the total number of viral genomes in the host.

The negative feedback system was linked to the “cro” gene, and was triggered by the overall lower rate of mRNA transcription present at this stage, and thus its protein products inhibited the genes responsible for the production of the lysogenic proteins, and so lysis takes place.

In case of co-infection by two or more viruses, as the overall level of viral mRNA transcription is higher (although the increase could be so small!)& the products activate the “c I” gene transcription, translated into lysogenic proteins that activate & accelerate the positive feedback system, leading to even higher levels of production of the lysogenic proteins, and the cell is kept alive and kicking for a certain time period.

The “c II” gene represents a “gate” to the activation of the lysogenic cascade, activated prior to the c I gene. This is a figure I designed to simplify the idea.

Although it is far from settled, but proposing the ability of viruses to make collective decisions based on the number of viral genomes in the surrounding environment can be a very important “life” history trait. Having this trait may be critical to the evolution and survival of certain types of viruses and can explain a lot about that. But what I thought to be most interesting is this: knowing about these mechanisms can allow us to manipulate them in the future! We might be able to slow down the aggressiveness of some viral infections by driving them to latency. Even if is not a radical cure, it can greatly improve the life quality of lots of patients. Maybe in the future we would be able to find other viral functions that are driven by the same mechanisms like host resource usage or cellular penetration, and so defeating viruses in some new unconventional ways…..so let us hope and work!

Source: www.esciencenews.com

Original paper: collective decision making in bacterial viruses

Biophysical journal 15 Sept 2008 (available online)

References (Citation by ResearchBlogging)
WEITZ, J., MILEYKO, Y., JOH, R., & VOIT, E. (2008). Collective Decision Making in Bacterial Viruses☆ Biophysical Journal, 95 (6), 2673-2680 DOI: 10.1529/biophysj.108.133694

Edited on Sep 24, 2010 (07:21 CLT)

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