Exploring new research to combat disease-causing viruses

August 3, 2018 by Elsa Rousseau, IBM
Mathematical and computational modeling of virus and defective particles competition at single cell, tissue, organ and host level will allow inference of antiviral design principles. These principles are then used to engineer the defective particle in the lab. Credit: IBM

According to the US Center for Disease Control, the number of worldwide cases of poliomyelitis has decreased from 350,000 in 1988 to 407 in 2013. While the decline has been steady, polio has still not been eradicated. To try and help solve the problem, biologists and mathematicians from IBM, UCSF, Stanford University, and the University of Haifa are working side-by-side on a DARPA-funded research project to engineer a new type of antiviral agent against viruses such as polio.

I recently joined IBM Research from Inria, the French National Institute for computer science and applied mathematics, where I was studying the durability of plant resistance to viruses. My transition to study human pathogens has been fascinating as I have been able to create a common language for our team to help bridge the gap between biology, math and informatics.

Our research team will focus on establishing design principles to engineer potential relying on Defective Interfering Particles (DIPs). They are defective versions of viruses, lacking essential elements to complete their life cycle. When co-occurring with their parent, -causing viruses, DIPs act as parasites by stealing the very essential elements they lack. This interference hinders the parent virus and enables the antiviral agents to replicate and spread, until the virus is completely gone and no more of the essential elements the agents lack remain available. After displacing the virus, the antiviral agents will die out because of their inability to survive alone. Defective versions of viruses naturally occur because of errors during viral replication; they have been observed, for example, in influenza A, dengue, and Ebola and are, in some cases, maintained in virus populations. Our team of researchers aims to produce models, which could potentially aid medical researchers to engineer DIPs that lack specific elements and are optimized for specific features, so they might be used as an efficient therapy. For this task, IBM researchers will use massive computational power and contribute their recognized expertise in mathematical modeling of diseases to help renowned world-class experimental and theoretical biologists at UCSF, Stanford University, and the University of Haifa.

Unlike existing drugs that stop by blocking known viral or cellular processes, DIPs can compete and co-evolve along with viruses. Like DIPs, vaccines also use a defective version of viruses, but as a preventive treatment building immune memory rather than a curative treatment based on competition and co-evolution. One interesting area for future exploration is whether the transmission mechanisms of DIPs between individuals might allow for new methodologies of health care delivery.

The research collaboration will focus on poliovirus, the virus responsible for poliomyelitis, a highly infectious disease that mainly affects children, and 1 in 200 infections leads to irreversible paralysis. In 1988, the Forty-first World Health Assembly adopted a resolution for the worldwide eradication of polio. It marked the launch of the Global Polio Eradication Initiative (GPEI). Wild poliovirus cases have decreased from an estimated 350,000 cases in more than 125 endemic countries then, to 22 reported cases in 2017. Endemic transmission is continuing in Afghanistan, Nigeria and Pakistan1.

An ongoing problem preventing full eradication of the disease is the occurrence of vaccine-derived poliovirus, a new instance of the disease caused when the vaccine strain mixes with other closely related viral species. It represents a serious threat to public health. Unfortunately, vaccine-derived poliovirus types have emerged in several places, mainly Democratic Republic of Congo, Nigeria, Syrian Arab Republic, and Pakistan.

The project proposed by IBM researchers and our collaborators could point the way forward for exploring new methods to help accelerate disease eradication in the face of vaccine-derived poliovirus. The defective and parasitic nature of DIPs may someday be used to reduce and even completely suppress the occurrence of the vaccine-derived disease types, while also helping to prevent the from spreading just as effectively as with traditional vaccines.

Our goal is to help extend this idea to other viral species to develop a general strategy, which might be used by public health actors for eradication of all viral diseases.

Explore further: On the brink of eradication: Why polio research matters

More information: Kia Guarino et al. Violence, insecurity, and the risk of polio: A systematic analysis, PLOS ONE (2017). DOI: 10.1371/journal.pone.0185577

Margarita Pons-Salort et al. Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame, PLOS Pathogens (2016). DOI: 10.1371/journal.ppat.1005728

Our Progress Against Polio. www.cdc.gov/polio/progress/index.htm

Related Stories

On the brink of eradication: Why polio research matters

April 20, 2017
In the decades since Dr. Jonas Salk developed the first polio vaccine, cases of polio have exponentially declined. Though once widespread epidemic, the highly infectious childhood disease is now close to global eradication. ...

Inching closer to a world without polio

March 23, 2018
At its height in the 1940s and '50s, polio paralyzed more than 35,000 Americans every year. But thanks to vaccines as well as good hygiene and sanitation practices, polio has largely been forgotten in the developed world.

Update on global polio eradication and the polio vaccine

October 16, 2015
Shortly after the successful global Smallpox Eradication Programme (SEP) in the 80's, world leaders and public health officials announced a plan to eradicate poliomyelitis (polio) off the face of the Earth; the Pan American ...

Polio vaccination: Paper highlights final steps to polio eradication

April 2, 2015
April 12th 2015 marks the 60th anniversary of the publication of Jonas Salk's landmark polio vaccine trial results, which confirmed that the first vaccine against polio was safe and effective. A new review, which was published ...

Combating antiviral drug resistance with dynamic therapeutics

August 24, 2017
Antiviral drug resistance has long been a problem in modern society. As viruses evolve, they develop resistance to antiviral drugs, which become less effective at treating diseases such as influenza.

Is the end of polio truly in sight?

November 30, 2011
Declaring the eradication of polio will be far more difficult than it was for smallpox, according to a review published in the Journal of General Virology. Further research into the complex virus - host interactions and how ...

Recommended for you

A versatile vaccine that can protect mice from emerging tick-borne viruses

December 18, 2018
A group of researchers led by Michael Diamond of Washington University School of Medicine in St. Louis have developed a vaccine that is effective in mice against Powassan virus, an emerging tick-borne virus that can cause ...

How cholera bacteria make people so sick

December 18, 2018
The enormous adaptability of the cholera bacterium explains why it is able to claim so many victims. Professor Ariane Briegel from the Leiden Institute of Biology has now discovered that this adaptability is due to rapid ...

Green leafy vegetables may prevent liver steatosis

December 17, 2018
A larger portion of green leafy vegetables in the diet may reduce the risk of developing liver steatosis, or fatty liver. In a study published in PNAS researchers from Karolinska Institutet in Sweden show how a larger intake ...

Discovery of novel mechanisms that cause migraines

December 17, 2018
Researchers at CNRS, Université Côte d'Azur and Inserm have demonstrated a new mechanism related to the onset of migraine. They found how a mutation that causes dysfunction in a protein which inhibits neuronal electrical ...

RNA processing and antiviral immunity

December 14, 2018
The RIG-I like receptors (RLRs) are intracellular enzyme sentries that detect viral infection and initiate a first line of antiviral defense. The cellular molecules that activate RLRs in vivo are not clear.

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.