Temperature plays crucial role in virus DNA release and infection

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Researchers at Lund University, together with colleagues at the NIST Synchrotron Facility in the US, have mapped at the atomic level what happens to virus particles when the temperature is raised.

“When the temperature rises, the genetic material of the virus changes its form and density, becoming more fluid, which leads to faster injection into cells,” said Alex Ivilevich, a researcher at Lund University who led the study.

Viruses do not have their own metabolism and the ability to replicate independently; They are completely dependent on a host cell for reproduction. Instead, the virus hijacks the internal machinery of infected cells to create new virus particles, which are then released and spread to infect other cells.

In most cases, the genetic material of the virus, the DNA, is enclosed in a protective protein shell called the capsid. A research team at Lund University is working to understand the process by which the virus releases its genetic material from the capsid and into the cell, and what causes the virus’s DNA to be released. It all started with a study published in 2014, in which researchers from Lund University found that the genetic material of the virus appears to suddenly change when exposed to temperatures of around 37 degrees.

The more we raised the temperature, the harder the DNA of the virus became. And then suddenly, at transmission temperature, something happened. “It was as if there was no DNA left in the virus particle—the rigidity had disappeared.”

Alex Ivilevich, professor of cell biology at Lund University

Can changes in ambient temperature affect the spread of virus DNA? The study has gained significant attention in the research community, but detailing what happened is challenging and time-consuming. As an experimental model, the researchers examined what happens when phage viruses—viruses that attack bacteria—are exposed to increased temperatures.

“Observing the appearance of DNA in virus particles is not something that can be done in an instant. Their genetic material is delicate, difficult to image, and moreover, phage viruses are very small – about ten times smaller than a bacterial cell. However, NIST’s synchrotron in Maryland, USA With the help of research facilities and a special grant from the Swedish Research Council, we were finally able to use neutron light to image the structure of phage virus DNA and its concentration inside the capsid. See how these change at different temperatures,” explained Alex Ivilevich.

In the current study, now published in PNAS, they show that ambient temperature plays an important role in when the capsid opens and the DNA “bursts” and enters the cell. The cell is infected so that phage virus particles can divide and spread to neighboring bacterial cells.

“We also observed that changes in DNA structure are directly linked to how effective the virus is at infecting host cells,” commented Alex Ivilevich.

Researchers’ interest in how virus capsids and DNA work is driven in part by understanding how DNA and RNA can be packed into such incredibly small volumes and injected into cells so quickly during infection.

“It gives us a greater understanding of how quickly DNA can come out of the virus and enter the cell, and may be relevant to how one can turn the virus on and off—fundamental principles for developing new antiviral agents. It may also have implications for gene therapy. How nucleic acids are packaged for purpose,” says Alex Ivilevich.

Could the study be interpreted as a higher body temperature increasing the risk of spreading the infection?

“The results point in that direction. The structure of the genetic material of the virus and its mechanical properties already change when the body temperature rises to 37 degrees. We also see that the increase in temperature affects the speed of the spread of the virus. However, we did so. This is only in our laboratory cells. was demonstrated in culture, and future studies are needed, taking into account other factors that influence the speed of infection, such as the immune response.”


Journal Reference:

i amValencia, JRV (2023). Temperature-induced DNA density transitions in phage λ capsids revealed with contrast-matching SANS. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2220518120.

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