Rift Valley Virus: NMR clues

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  • Published: May 15, 2015
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Rift Valley Virus: NMR clues

Mutatingly virulent

Damming and Damning Haemorrhagic Diseases (Credit: University of Montreal)

A US team has used NMR spectroscopy to investigate the structural properties of an important protein of the Rift Valley fever virus, a virus that causes infections in both humans and livestock (cows, sheep, goats and camels) similar to the Ebola virus, although it is spread through touching infected animal blood, breathing in the air around an infected animal being butchered, drinking raw milk from an infected animal, or being bitten by an infected mosquito; human to human transmission has not been observed.

The recent Ebola outbreaks reveal just how worrying haemorrhagic fever viruses can be. These diseases present a dramatic risk to human health as they often spread quickly and kill a high percentage of infected individuals. They are like other diseases self-limiting but can kill tens of thousands of people before an epidemic subsides and then only if strict hygiene and healthcare protocols are adhered to in affected areas. Unfortunately, there are no effective drug therapies nor vaccines available for the majority of these lethal viruses. That issues is partly one of the outbreaks most commonly occurring in developing countries with limited financial resources and thus limited incentive on the part of conventional pharmaceutical companies to invest. However, it is not simply a matter of socioeconomics. The genomes of haemorrhagic fever viruses can mutate quickly, which means they can become resistant to any potential drug treatment introduced into the ecosystem. Moreover, this mutability means they can also evade the advances of the immune system weaponry. Currently human protection against Rift Valley virus is based on vaccinating animals against the disease.

Finding binding blockers

Normand Cyr of the University of Montreal's Department of Biochemistry and Molecular Medicine, and colleagues are investigating the virulence of a well-known haemorrhagic fever virus, Rift Valley fever virus. “Although our work does not directly lead to treatments on a short term, it does identify a process where the virus could be vulnerable to drug therapy, or how we might design an attenuated viral strain for vaccine development,” he explains. “Identification of the Achilles heels of haemorrhagic fever viruses will help inspire additional research and eventually lead to the development of new therapeutic strategies to treat these deadly tropical infections.”

Cyr works under the academic supervision of James Omichinski and they provide details of the research in the journal Proceedings of the National Academy of Sciences of the USA. “Our group used NMR spectroscopy - three-dimensional 15N-edited NOESY-HSQC and 13C-edited HSQC-NOESY - to investigate the structural properties of an important viral protein required for virulence of the Rift Valley fever virus, a virus that causes infections in both humans and livestock similar to the Ebola virus,” Omichinski explains. “Viral proteins such as the Non-structural protein (NSs) studied here bind to the transcription machinery of human cells via the p62 subunit of the TFIIH protein complex, which leads to the formation of nuclear filaments that are essential for propagation of the virus." He adds that, "The structural details reported show that the viral protein uses a simple so-called Omega-XaV motif that is similar to that found in human DNA repair proteins, and blocking this binding event with drugs would certainly weaken the virulence of the virus.”

North American frontier

The University of Montreal team worked with Kylene Kehn-Hall’s group at the National Center for Biodefense and Infectious Diseases in the USA, a team has specialist biosafety level 3 facilities where they can work with such contagious viruses.

Americans and Canadians alike have every reason to be concerned about the future of this line of research. “Climate changes and world-wide travel are increasing the risk of haemorrhagic fever viruses even in Canada," says Omichinski. "We cannot afford to ignore the global health status of populations in other countries. It is therefore critical that we gain more knowledge into the molecular details of viral function so that we can develop more effective treatments and control the spread of these diseases," he adds.

Related Links

Proc Natl Acad Sci 2015, 112, 6021-6026: "A motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence"

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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