Spaghetti virus: NMR clues to cancer-causing herpes

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  • Published: Mar 1, 2014
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Spaghetti virus: NMR clues to cancer-causing herpes

Spaghetti virus

NMR spectroscopy research carried out at Manchester University has revealed that herpes virus proteins are more

NMR spectroscopy research carried out at Manchester University has revealed that herpes virus proteins are more "spaghetti-like" than previously thought. The discovery hints at possible treatments for a form of the disease that causes the cancer known as Kaposi’s sarcoma. The team has shown that the virus protein uses its flexible arms to pass on viral building blocks to the proteins of cells that it hijacks. Alexander Golovanov and colleagues provide details in the journal PLoS Pathogens.

"Viruses cannot survive or replicate on their own - they need the resources and apparatus within a host cell to do so," explains Golovanov. The new research provides the first ever molecular insight into how the herpes virus RNA is transferred between viral and cellular proteins, thus helping the virus to hijack a cell. The research, funded by the UK's Biotechnology and Biological Sciences Research Council (BBSRC), used a new methodology to reveal exactly how these flexible proteins interact with RNA in squirrel monkey herpes virus as it infects mouse cells. The NMR data allowed them to construct a three-dimensional model of the interacting system. The monkey virus is closely related to the form of herpes virus 8 that leads to the rare human cancer, Kaposi's sarcoma.

Soft-boiled locks and keys

Golovanov likens the protein interactions to having a key made from boiled spaghetti and yet still managing to open a rigid lock. "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 to perform a defined complex function, despite lacking rigidity. The viral proteins behave a lot like such spaghetti."

Sarcoma insights

There is currently no effective antiviral treatment against viral replication but finding a weak spot in the viral infection and replication process might be able to prevent Kaposi's sarcoma from developing. Kaposi's sarcoma was originally identified in 1872 by its eponymous discoverer Hungarian dermatologist Moritz Kaposi working at the University of Vienna. Classically, it is seen in people of Jewish and Arabic descent. However, a variant on the disease became associated with the emergence of HIV/AIDS in the 1980s as infection arises in non-classical populations with compromised immune systems. A clearer understanding of how the herpes virus functions might lead to novel treatments for this illness.

"We are continuing to research the mechanisms underlying how a herpes virus takes control of the cellular pathways at a sub-molecular level," team member Richard Tunnicliffe told SpectroscopyNOW. "The next step is applying the lessons and techniques from [this] work to other interactions in related viral species - it will be interesting to learn if these fuzzy protein complexes are a common feature. Our long-term goal is to innovate how we study protein interactions and to use the knowledge we gain along the way, it would be great to try and disrupt the interactions of these viral proteins and help treat the disease."

Related Links

PLOS Pathogens, 2014, online: "Competitive and Cooperative Interactions Mediate RNA Transfer from Herpesvirus Saimiri ORF57 to the Mammalian Export Adaptor ALYREF"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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