Herpes virus in incredible detail
Image: Highly ordered DNA packaged in the common herpes virus. [from McElwee et al, PLOS Biology, June 20, 2018]
Scotland-based researchers have used cryo-electron microscopy to reveal the detailed structure and biological mechanism of the common herpes virus.
The herpes family includes the viruses that cause both cold-sores and chicken pox as well as viruses that can cause cancers and severe illnesses in the unborn child.
However, researchers have struggled to analyse the herpes virus shell - home to the DNA that infects a host - as it is only 100 nm in diameter.
Given this, Dr David Bhella from the MRC-University of Glasgow Centre for Virus Research and colleagues imaged virus preparations using an FEI Titan cryo-TEM at the UK national cryoEM facility - eBIC - at Diamond Light Source.
CryoEM and 3D image reconstruction of HSV-1 virions: views of unsharpened 3D reconstructions and close-up stereo pair images of the penton and portal vertices. Imposition of full icosahedral symmetry led to the calculation of a map at 6.3 angstroms resolution, [McElwee et al, PLOS Biology, June 20, 2018]
Images of the capsid were captured at a nominal magnification of X 81,000 with 'movies' of the virus recorded on a Falcon III camera with sampling of 1.78 Å/pixel.
Analyses revealed the structure of a motor-like assembly called a portal, responsible for virus replication.
The structure of the virus's portal-vertex interior: a central slice through a reconstruction of the HSV-1 virion reveals the internal features of its portal-vertex. A strong linear density (a) is seen to run through the portal-vertex that is attributed to genomic DNA (white arrow). Click here for more detail, [McElwee et al, PLOS Biology, June 20, 2018]
As the researchers explain, the Herpes virus pumps DNA into preassembled capsids through this molecular machine, which is also used to eject DNA into the host.
“Cryo-electron microscopy, combined with new computational image processing methods, allowed us to reveal the detailed structure of the unique machinery by which the virus packs DNA into the capsid," highlights Bhella. "The DNA is packed very tightly, reaching a pressure similar to that inside a bottle of Champagne."
As well as detailing the shape of the portal machinery, the researchers also determined how the virus packs its DNA inside the capsid, showing how individual strands of DNA are wound up in a spool, rather like a ball of wool.
DNA packaging in HSV-1: the unsharpened reconstruction of HSV-1 is presented showing a series of radially cropped views of the interior density; these reveal the highly ordered arrangement of packaged DNA. The outermost (a), second (c), and third (e) shells are shown, revealing a left-handed spool of density. Spherical sections of each shell are also presented (b,d,f). [McElwee et al, PLOS Biology, June 20, 2018]
The development of cryo-EM as a technique for resolving detailed atomic structures was developed at the MRC Laboratory of Molecular Biology.
“We hope that this study will eventually lead to the development of new medicines to treat acute herpes virus infections, through the design of drugs that will block the action of the portal motor,” says Bhella.
Research is published in PLOS Biology.