Viruses can convert their DNA from solid to liquid from, Liquid DNA behind virus attacks



Date: October 6, 2014

Source: Lund University



Viruses can convert their DNA from solid to fluid form, which explains how viruses manage to eject DNA into the cells of their victims. This has been shown in two new studies carried out by Lund University in Sweden.


Both research studies are about the same discovery made for two different viruses, namely that viruses can convert their DNA to liquid form at the moment of infection. Thanks to this conversion, the virus can more easily transfer its DNA into the cells of its victim, which thus become infected. One of the studies investigated the herpes virus, which infects humans.


"Our results explain the mechanism behind herpes infection by showing how the DNA of the virus enters the cell," said Alex Evilevitch, a researcher in biochemistry and biophysics at Lund University and Carnegie Mellon University.


Evilevitch stated that the discovery was surprising. No one was previously aware of the 'phase transition' from solid to fluid form in virus DNA. The phase transition for the studied herpes virus is temperature-dependent and takes place at 37<C, which is a direct adaptation to human body temperature. Evilevitch hopes that the research findings will lead to a new type of medicine that targets the phase transition for virus DNA, which could then reduce the infection capability and limit the spread of the virus.


"A drug of this type affects the physical properties of the virus's DNA, which means that the drug can resist the virus's mutations," said Alex Evilevitch.


The second study that Evilevitch and his colleagues have published recently is about bacteriophages, i.e. viruses that infect bacteria, in this case E coli bacteria in the human gastrointestinal tract. The results show that this virus also has the ability to convert its DNA from solid to fluid form. As with the herpes virus, the phase transition takes place at 37<C, i.e. adapted to human body temperature.


These two virus types, bacteriophages and the herpes virus, separated at an early stage in evolution, several billion years ago. The fact that they both demonstrate the same ability to convert their DNA in order to facilitate infection indicates that this could be a general mechanism found in many types of virus.


In previous studies, Alex Evilevitch and his colleagues have succeeded in measuring the DNA pressure inside the virus that provides the driving force for infection. The pressure is five times higher than in an unopened champagne bottle. This high pressure is generated by very tightly packed DNA inside the virus. The pressure serves as a trigger that enables the virus to eject its DNA into a cell in the host organism. It was this discovery that led to the two present studies, which were recently published in Nature Chemical Biology and PNAS.




We discovered that dsDNA in phage λ-capsids undergoes a solid-to-fluidClike transition as a result of decreased genome ordering occurring close to the optimum temperature for infection in the environment of the human host (i.e., 37 <C). This finding explains how a tightly packed, kinetically trapped encapsidated viral genome (21) can be ejected readily into the cell. To our knowledge, this is the first demonstration of viral metastability attributed to the genome rather than the capsid. Because phage infectivity in vivo is significantly affected by the efficiency of viral DNA translocation into the cell (11, 14), the metastable state of the tightly packaged DNA likely is rate limiting for the viral replication cycle. Thus, at lower temperatures outside the host, the DNA in the capsid is solid-like with restricted mobility, which helps prevent its spontaneous release. Once inside the host, the increased temperature induces the necessary mobility of the viral genome, facilitating its infection of bacterial cells. This demonstrates an evolutionary physical adaptation of viruses to their host environment. We recently found for human herpes simplex virus that its intracapsid stressed DNA state leads to pressure-driven DNA ejection analogous to that of phage λ (6). This observation suggests that this unique metastable state of DNA in viral capsids may be universal for many pressurized viruses and may serve as a new target for drugs interfering with viral replication.