Contact Details

Oxford Particle Imaging Centre,
Division of Structural Biology,
Henry Wellcome Building for Genomic Medicine,
Oxford, OX3 7BN, UK

Telephone: (+44) (0)1865 287844
E-mail: juha@strubi.ox.ac.uk

Research Areas

My group focuses on structures and host cell interactions of emerging viruses.

We study how viruses belonging to viral family Bunyaviridae infect their host cells. Many Bunyaviruses are pathogens causing serious diseases. These include Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus and many hantaviruses. Despite the medical importance of bunyaviruses, very little is known about their detailed three-dimensional structures and infection mechanisms. We use mainly electron cryo-microscopy, combined with computational 3D reconstruction methods, to solve the structures of mature virions, and intermediate structures existing during entry, membrane fusion and maturation.

In our first study, we used electron cryo-tomography to solve the first structure of a Bunyavirus using an apathogenic Uukuniemi virus (Phlebovirus, Bunyaviridae) as a model system using (Överby et al. 2008 PNAS). The tomographic reconstructions revealed two different conformations of the glycoprotein spikes, and these were shown to be pH dependent. Similar pH-dependency in the conformations of glycoprotein spikes is seen in many other virus systems, such as Dengue virus (flavivirus), and this may help to understand the infection mechanism of Bunyaviruses as well.

In our second study, the analysis of Rift Valley fever virus (Phlebovirus, Bunyaviridae) particles showed that they were well preserved during purification. Electron cryo-microscopy showed that the particles were homogeneous in their size and shape. Thus we were able to apply single particle averaging approach, combining data together from multiple particles. This approach yielded a much high resolution (2.2 nm) that was possible for Uukuniemi virus and helped us to understand the organization of the glycoproteins, which are responsible for host cell binding and membrane fusion (Huiskonen et al. 2009 J Virol).

The infection of a host cell by a virus is a complicated process and its study requires a combination of different techniques and model systems. Our electron cryo-microscopy and tomography studies will be combined with other complementary imaging and biophysical techniques to yield a detailed description of Bunyavirus infection. For example, we are combining electron tomography of infected cells with light microscopy of GFP-labeled particles and high-resolution single particle electron cryo-microscopy with fitting of X-ray structures of viral glycoproteins into density maps of whole virus particles.

The work is carried out in the containment facility of Oxford Particle Imaging Centre, which provides facilities for virus production and high resolution electron cryo-microscopy and tomography.