Herpes treatment – A step closer in fight against cancer-causing herpes.

Herpes Viruses necessary proteins are more ‘spaghetti-like’ than previously thought, which provides a vital hint in the search for an effective treatment against a type of herpes which causes a form of cancer known as Kaposi’s sarcoma. That’s according to scientists from The University of Manchester who have found that herpes proteins uses its versatile hands to successfully transfer popular foundations to the necessary proteins of tissues that it hijacks.

The latest part of this research is released in the Feb version of PLoS Pathogen which has discovered how the proteins of tissues hi-jacked by the viruses take on a ‘spaghetti-like’ structure.

The research provides the first ever molecular understanding of how the virus RNA, a type of compound which allows decoding the generic blueprint of a viruses, is transferred between viral and cellular protein, thus assisting the virus to hijack a cell. Dr Tunnicliffe, the first author, said: “Viruses cannot survive or replicate on their own — they need the resources and apparatus within a host cell to do so.”

In their research, financed by the Biotechnology and Biological Sciences Research Council, the study team developed and used a new technique which exposed how exactly versatile necessary protein interact together and with RNA.

Dr Tunnicliffe continues: “We have designed a novel strategy which shows how versatile molucules perform together; this gave us a glance of how the virus is able to get the workings of the cell that it infects.”

The research team has been using NMR — a technique related to the one used in MRI body scanners and capable of visualising elements at the smallest scales — to analyze how small elements of herpes virus help it to increase by binding themselves with other large molecules; this created pictures of a monkey herpes virus proteins mouse cellular proteins and viral RNA. These pictures were then used to create a 3D design of how viral RNA is recognised by this herpes virus protein and then then passed on to the cellular protein of the host.

Although the design system analyzed here used proteins from a varieties of herpes viruses — which is only passed on between squirrel monkeys, without actually doing much damage to them — these herpes viruses are very similar to virus resulting in Kaposi’s sarcoma in people. Knowing how monkey virus work may help to figure out ways to prevent this type of cancer in people.

Senior researcher Dr Alexander Golovanov, from the Manchester Institute of Biotechnology and Faculty of Life Sciences, said: “Initially proteins were thought to interact only as fitting rigid bodies — as a lock and key, for example. The fitting key is inserted into the lock, and that sets the rigid mechanism of a lock in action. Then the understanding evolved — it was found that not all protein ‘keys’ is rigid, some are more like boiled spaghetti which can still operate the rigid lock successfully, by adjusting its shape.”

Dr Golovanov continues: “Just recently, the ‘fuzzy’ protein complexes were discovered — it is as if not only the ‘key’ is made of flexible boiled spaghetti, but also parts of the lock itself are made of boiled spaghetti. This ‘spaghetti mechanism’ still manages perform a defined complex function, despite lacking rigidity. The viral proteins behave a lot like such spaghetti.”

He added: “Unfortunately, no effective antiviral treatment is currently available, which suppress viral replication efficiently enough. Finding a weak spot in the virus, which can be used to prevent Kaposi’s sarcoma in the future, therefore would make a significant breakthrough.”

Professor Melanie Welham, BBSRC Executive Director of Science, said: “This is an interesting technique which will help us understand more about the herpes virus and could be applied in virology research more generally. This is the type of excellent bioscience research underpinning health that BBSRC seeks to fund to deliver social and economic benefits for all.”


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