Recent Research Highlights

Here you will find very brief summaries of recently published papers from our lab. I've tried to condense the text down to a 'take-home-message', and if you'd like to know more, the full papers are accessible from my home page, under the 'publications' tab. These papers are all open access so you should have no problems getting hold of them.

We recently published the crystal structure of the Hazara virus nucleocapsid protein (Surtees et al, 2015). The take home messages in this paper are firstly, that the N protein structure is virtually identical to that from its close-cousin CCHFV, and secondly, that HAZV N also has an interesting caspase cleavage site at the arm apex, even though the sequence of this site differs from that on the CCHFV arm. Whether cleavage at this site has a functional role in the nairovirus life cycle is unknown. The close structural homology that this study has revealed between HAZV and CCHFV further supports the use of HAZV as a good model for certain aspects of the nairovirus life cycle.

Viruses all need to occupy a host in order to multiply and this is because they need to subvert cellular processess and consume cellular resources as building blocks for their own anabolism. As part of this programmed way of  'life' they interact with cellular components, and co-opt their machinery. A couple of recent papers of ours describes some of these interactions:

The first of these (Hover et al, JBC, 2016) describes how Bunyamwera virus (BUNV) has a critical dependance on K+ ion homeostasis during the early stages of the life cycle, such that when certain K+ conducting ion channels are blocked by specific compounds, BUNV can no longer multiply. We measure virus growth by detecting the synthesis of newly made N protein by western blot, and this shows that when specific channel blockers are applied up to about 6 hours post infection, BUNV growth is prevented (see BUNV anti-N western blot below). In the paper we describe how we think this K+ dependance comes into play during movement of the virus through the endocytic machinery.

The second of these papers (Surtees et al, Journal of Virology, 2016) describes the interaction between the nairovirus nucleocapsid protein and a whole host of cell proteins, determined using a global proteomics approach from both infected cell lysates and also purified virus. We focussed on one group of these cell proteins called heat shock proteins, for which the native cellular role is to assist in correct protein folding. We used a range of biochemical and cell biology techniques to further probe this interaction, and one of the most interesting outcomes was that HSP70 and HSP90 family members interact with N both in cells and also inside purified virus particles (see western blot image below). Why this should be the case we don't yet now.