Mutual exclusion occurs when a host cell is simultaneously infected with two competing viruses, but only one virus goes on to replicate itself. This phenomenon was originally described in bacteriophages by Delbrück in 1945. Mutual exclusion implies that the virus particle which infects first alters the host cell in such a way that a second infection is unlikely. Subsequent studies found that mutual exclusion not only occurs between different viruses but also with nearly identical viruses, presumably as a way to avoid “super-infection” (Dulbecco, R. 1952 Mutual exclusion between related phages. J Bacteriol 63, 209-217). While the virus that wins the race prevents infection by additional viruses, the excluded viruses may interfere with its replication, which is referred to as a “depressor effect” (Delbrück M. 1945 Interference Between Bacterial Viruses: III. The Mutual Exclusion Effect and the Depressor Effect. J Bacteriol. 50(2): 151-170). There are different mechanisms underlying mutual exclusion and depression among bacteriophages, and still, not all of them are understood.
In some instances, exclusion causes the out-competed virus to be rapidly degraded. For example, with bacteriophage T3, degradation occurs after adsorption of the primary infecting phage but before the virus genome is expressed. There is indirect evidence with phage λ that host membrane depolarization is triggered by the successful infecting particle, which initiates exclusion.
Mutual exclusion not only occurs among bacteriophages but also in viruses infecting certain unicellular, eukaryotic chlorella-like green algae (the chlorella viruses). Plaques arising from single cells simultaneously inoculated with two different chlorella viruses usually only contain one of the two viruses. Previously, the mechanism underlying chlorella virus mutual exclusion is unknown. Chlorella viruses often encode DNA restriction endonucleases and it was originally suggested that one function of the DNA restriction endonucleases might be to exclude infection by other viruses. A new study indicates that chlorella viruses prevent multiple infections by depolarizing the host cell membrane (Chlorella Viruses Prevent Multiple Infections by Depolarizing the Host Membrane. J Gen Virol. Apr 22 2009).
The icosahedral shaped chlorella viruses initiate infection by attaching rapidly, specifically and irreversibly to their host cell wall, probably at a unique virus vertex (corner of the icosahedron). Attachment is immediately followed by cell wall degradation at the point of contact by a virus-packaged enzyme(s). Following wall degradation, the virus internal membrane fuses with the host membrane, facilitating entry of the virus DNA and virion-associated proteins into the cell, leaving an empty virus capsid attached to the cell wall. This process initiates rapid depolarization of the host membrane, triggered by a virus encoded potassium channel located in the virus internal membrane and the rapid release of potassium from the cell. The rapid loss of potassium and associated water fluxes from the host reduce cell turgor pressure, which may help entry of virus DNA into the host.
Two different chlorella viruses were used in the study because they can be distinguished by real time PCR and they have differential sensitivity to caesium, a well known potassium channel blocker. The results showed that virus-induced membrane depolarization was at least partially responsible for the exclusion phenomenon. And that’s how this virus stays one step ahead of its “friends”.
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