Poliovirus on Time

Poliovirus on TimePoliovirus has made the cover of Time magazine.

The Time cover image for the 14 January 2013 issue is a model of poliovirus bound to a soluble form of its cellular receptor, CD155. I was part of the team that solved the structure of this complex in 2000, together with the laboratories of Jim Hogle and Alasdair Steven. The structure of the same complex was also solved by Rossmann’s group. The image that Time used for the cover was produced by Laguna Design, although I do not know whether they used our structural information or Rossmann’s.

The Time cover image is accompanied by the text: One thing stands in the way of wiping out the virus for good: the Taliban. It’s a good thing for Time to highlight the polio eradication effort. However, as Alan Dove wrote to me, “I’m also glad to see from the headline that the Taliban is the only obstacle to eradication now. Would love to hear how they’ve solved the problems with vaccine derived strains, chronic secreters, finding all the remaining stocks, and covering Nigeria.”

The issue contains an article by Jeffrey Kluger, author of Splendid Solution: Jonas Salk and the Conquest of Polio. I wrote a review of the book for the Journal of Clinical Investigation, which is available online as an open access article.

When I visited the University of Michigan in 2011, Stefan Taube gave me a model of the poliovirus-receptor complex that he had produced on a three dimensional printer (photograph below). I think it would have looked better on the cover of Time.

Update: I do have a problem with the Time headline ‘Killing Polio’. How can you kill something that is not alive?
Poliovirus and receptor

Capturing viruses with bacteria

pvr ecoliWhen my laboratory discovered the cell receptor for poliovirus in 1989, many new research directions were suddenly revealed – such as creating a mouse model for poliomyelitis. One application we did not think of was to use the receptor to screen samples of drinking water for the presence of viruses.

Contamination of the water supply with fecal material can lead to the presence of enteric viruses, which constitute a public health risk. A variety of methods have been developed to screen for viruses in water samples using cell culture or nucleic acid detection techniques. Because the numbers of human viruses in water samples are low, a concentration step must usually be included. These are typically laborious and costly, and innovative improvements are needed. Enter CD155, the cellular receptor for poliovirus, which the authors used as a model for developing a new way to concentrate viruses from water samples.

Viral receptors, which are present on the surface of susceptible cells, are very efficient at capturing viral particles. Why not put these receptors on the surface of bacteria, where they can bind to viruses? Concentrating the viruses would then be a simple matter of centrifuging the bacteria from the water sample. This concept was tested by using poliovirus and the poliovirus receptor.

For this method to work, the viral receptor protein must be present on the surface of bacteria (Figure). To accomplish this goal, an artificial gene was made which codes for the poliovirus receptor protein fused to the ice nucleation protein (INP) gene. This protein is normally present on the surface of the bacterium Pseudomonas syringae.

When the PVR-INP gene was expressed in E. coli, the fusion protein was located to the surface of the bacteria, where it could bind poliovirus. The recovery efficiency was then tested by adding poliovirus to tap water, saline, and samples from several local rivers. The engineered bacteria were added to the poliovirus-laced waters and mixed for 20-60 minutes. The bacteria were then removed by low speed centrifugation, and the viral titers in the cell and in the liquid sample were determined by plaque assay. The recovery of infectious virus ranged from 99% (saline samples) to 75% (river water).

These findings demonstrate that recombinant bacterial cells can be used to capture virus particles in different types of water samples. Compared with other water concentration methods, centrifugation is inexpensive and easy. Whether or not this assay is sensitive enough to detect low levels of viruses in drinking water and other samples must still be determined.

In a way it is fitting that bacteria have been used to capture poliovirus. After all, poliovirus initially replicates in the gastrointestinal tract, where the microbial flora (including E. coli) helps the virus invade the host.

Abbaszadegan M, Alum A, Abbaszadegan H, Stout V. 2011. Cell surface display of poliovirus receptor on Escherichia coli, a novel method for concentrating viral particles in water. Appl Envir Micro 77:5141–5148.