Viruses change structure at the temperature of the human body to better infect us

Amazing stuff! Research across continents! Demystifying and defeating viruses one step at a time!

"In the latest work, [researchers from Lund University in Sweden] focused on phage viruses – that is, those that attack bacteria. Using neutrons from the synchrotron research facility at the US National Institute of Standards and Technology (NIST) in Gaithersburg, Maryland, they imaged the structure of the virus DNA and its density inside the capsid as a function of temperature.

“The technique we employed is called small-angle neutron scattering (SANS), which is not typically used for microbiology research,” says Evilevitch. “By exposing the phage bacterial viruses to the neutron beam, we could reveal the structural details of virally packaged DNA with atomic resolution.”
The researchers undertook this work to follow up their earlier discovery that the structure of DNA material inside the capsid undergoes a sudden structural change when exposed to a temperature of 37 °C. This is the normal temperature of the human body, and it implies that structure plays a central role the way the virus delivers its genetic material into a cell – the first step in an infection. ...

The Lund team is now optimizing its approach with neutron light to investigate density changes in DNA packaged in type-1 human Herpes virus. “This knowledge will be important for understanding the DNA ejection mechanism, which in turn may control the course of infection,” ... “This can be either latent (dormant) or lytic (active, and where the virus rapidly replicates).” ..."

From the significance and abstract:

"Significance

This work explains the structural origin of the temperature-dependent DNA density transition in bacteriophage λ capsid, occurring close to the physiological temperature favorable for infection (37 °C, human body temperature). Using small-angle neutron scattering, with contrast-matched scattering contribution from viral capsid proteins, we unveiled two coexisting DNA phases in a capsid—a hexagonally ordered high-density shell-DNA phase in the capsid periphery and a low-density, less-ordered DNA phase in the core. At the transition temperature, a density and volume transition occurs in the core-DNA, resulting in lower density and reduced packing defects. This yields increased mobility of the core-DNA phase, facilitating rapid DNA ejection events from phage into a host bacterial cell.

Abstract

Structural details of a genome packaged in a viral capsid are essential for understanding how the structural arrangement of a viral genome in a capsid controls its release dynamics during infection, which critically affects viral replication. We previously found a temperature-induced, solid-like to fluid-like mechanical transition of packaged λ-genome that leads to rapid DNA ejection. However, an understanding of the structural origin of this transition was lacking. Here, we use small-angle neutron scattering (SANS) to reveal the scattering form factor of dsDNA packaged in phage λ capsid by contrast matching the scattering signal from the viral capsid with deuterated buffer. We used small-angle X-ray scattering and cryoelectron microscopy reconstructions to determine the initial structural input parameters for intracapsid DNA, which allows accurate modeling of our SANS data. As result, we show a temperature-dependent density transition of intracapsid DNA occurring between two coexisting phases—a hexagonally ordered high-density DNA phase in the capsid periphery and a low-density, less-ordered DNA phase in the core. As the temperature is increased from 20 °C to 40 °C, we found that the core-DNA phase undergoes a density and volume transition close to the physiological temperature of infection (~37 °C). The transition yields a lower energy state of DNA in the capsid core due to lower density and reduced packing defects. This increases DNA mobility, which is required to initiate rapid genome ejection from the virus capsid into a host cell, causing infection. These data reconcile our earlier findings of mechanical DNA transition in phage."

Viruses change structure at the temperature of the human body to better infect us – Physics World

Temperature-induced DNA density transition in phage λ capsid revealed with contrast-matching SANS (open access)

Fig 1 (no title)