Influenza attack: Raman to reveal hijack

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  • Published: Mar 1, 2017
  • Author: David Bradley
  • Channels: Raman
thumbnail image: Influenza attack: Raman to reveal hijack

Particulates

Laura Fabris, associate professor in the Department of Materials Science and Engineering. Photo: Kate Woodside

Laura Fabris of Rutgers University, New Jersey, USA, and her colleagues are using surface enhanced Raman scattering (SERS) spectroscopy to investigate the role that might be played by TIPs - therapeutic interfering particles in defending us against influenza, flu.

TIPs might be used to target appropriate sites that would otherwise be attacked by viruses such as influenza, HIV, Ebola and others, the aim would be for those particles to infiltrate and compete more successfully than the viral particles. As part of the four-year, US$5.2 million INTERfering and Co-Evolving Prevention and Therapy (INTERCEPT) program, Fabris and her team will receive an US$820,000 grant from the Defense Advanced Research Projects Agency (DARPA) to see how gold nanoparticles might be used in SERS experiments for the first time in virology to image the influenza virus and monitor how mutations change the virus with unprecedented sensitivity as it enters host cells. Outbreaks of seasonal influenza have been high this winter any new research that can help medicine to address the disease in future outbreaks and epidemics is welcome.

"Before we can understand how to make these therapeutic particles, we need to understand how viral mutation works, explains Fabris who is an associate professor in the Department of Materials Science and Engineering at Rutgers.

Influenza ongoing

As part of its ongoing research, DARPA hopes to harness TIPs, which are tiny virus-like entities with engineered genetic material that encodes defective viral proteins. As with regular viruses, TIPs can enter host cells, but because they do not carry with them the necessary genetic information they cannot replicate in those cells, unless the cells are already infected with a virus. An additional point to note is that RNA viruses including influenza have a protein-studded coating, a membrane envelope. In a cell infected with both an influenza virus and a TIP, the cell makes copies of the TIP genome that compete for viral proteins. The goal is to ensure that the harmless TIPs outnumber influenza particles by taking up resources that the virus would otherwise exploit in the host cell. The cells would generate lots of dud viruses, the TIPs at the expense of the actual pathogenic virus and so inhibit the infection and its associated symptoms as well as the ability of the virus to spread. The TIP genes would essentially diluted the harmful viruses and halt any infection in its tracks...in theory.

Imaging effort

In early studies, researchers have demonstrated that TIPs applied to cultured host cells can reduce viral count by almost twenty times. Within the INTERCEPT program, which is hoping to boost antiviral efforts, TIP safety tests and an examination of efficacy in animal models will be undertaken. There is also the question of whether or TIPs can keep pace with the ever-changing genetic character of active viruses, which are successful partly because spontaneous mutations allow them to evolve a response to the host's immune defences for instance.

"Ideally, the TIPs will be introduced into influenza virus populations and compete for protein, so the virus will starve and not be able to reproduce," Fabris explains. Within the INTERCEPT program, Fabris' team will work alongside virologists, evolutionary biologists and mathematicians from North Carolina State University (Ruian Ke), Duke University (Katia Koelle), University of Illinois at Urbana-Champaign (Christopher Brooke), and Montana State University (Connie Chang). The focus is on finding out how the virus mutates at the cellular, animal and population levels. Fabris will specifically provide imaging and quantification methods using SERS to obtain chemical composition and structure within the virology work.

Fabris has used SERS for eleven years and will be using gold nanoparticles to examine and quantify what is happening within host cells when TIPs and viral particles are present. "Our research will have repercussions, for example, in how to do sequencing of genes in a way that is cheaper and deeper compared with traditional sequencing," Fabris adds.

Related Links

Bioanal 2015, earlier work: "SERS-based approaches toward genetic profiling"

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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