TWiEVO 5: Looking at straw colored fruit bats through a straw

TWiEVOOn episode #5 of the science show This Week in Evolution, Sara Sawyer and Kartik Chandran join Nels and Vincent to talk about how the filovirus receptor NPC1 regulates Ebolavirus susceptibility in bats.

You can find TWiEVO #5 at microbe.tv/twievo, or you can listen below.

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TWiV 363: Eat flu and dyad

On episode #363 of the science show This Week in Virology, The TWiVers reveal influenza virus replication in the ferret mammary gland and spread to a nursing infant, and selection of transmissible influenza viruses in the soft palate.

You can find TWiV #363 at www.microbe.tv/twiv.

Viral supercomputer simulations

Jason Roberts, a virologist at the Victorian Infectious Disease Reference Laboratory in Melbourne, Australia, creates three-dimensional simulations of viruses showing how the molecules that make up the capsid and genome might move in very short periods of time. I visited Jason in his laboratory at the newly constructed Peter Doherty Institute, to learn how he develops these simulations. Then I toured the Peak Computing Facility, which houses the supercomputer that calculates Jason’s simulations.

 

Virology question of the week

HIV binding CD4 and ccrOn the science show This Week in Virology we receive many questions and comments, which are read every week. I also get many questions here on virology blog, which I tend to answer by email. However I think that everyone could benefit from these questions, so I’ve decided to post one here each week along with my answer.

This week’s question is from Joseph, who wrote:

I’m relatively new to virology or anything biology-related. Hell, I’m studying computer science as an undergrad at the moment; however, there’s something about virology that fascinates me – the simplistic fact that we can’t cure viruses, which are less complex than bacterium (in which we can treat, and they’ll eventually pack their bags and leave).

I’ll get to my question … since most, if not all, cells in the body replicate and reproduce and none of them merge, why do our cells let virions in? You would think after years of viral/immune system encounters, our bodies would have adapted to repelling these viruses off. I understand it’s probably much more complicated than that, but I would love to hear your answer. Does it have anything to do with virions’ size being so small?

This is a great question. In fact, I had a similar question on a midterm examination in my virology course. I phrased it this way: Could cells evolve to not have receptors for binding viruses?

I sent this answer to Joseph:

Viruses get into cells by binding to proteins on the cell surface – viruses have evolved to do this: they are safecrackers.

You would think that the cells would evolve to change these proteins – and you would be right. Over thousands of years, the cell proteins change, so the viruses can’t bind anymore.

But guess what? The viruses change right back so that they can bind to the cell protein once more.

Now you might ask: why doesn’t the cell get rid of that surface protein? The answer there is that they are needed for the cell, so they can’t be removed.

There seems to be one exception to the last statement: about 4-16% of people of Northern European descent don’t make one of the receptors for HIV. They are resistant to infection. But this doesn’t happen for most other viruses.

Joseph wrote back:

Hmm. I thought by definition virions weren’t living organisms, yet they “adapt” to bind to living cells. Sounds like those emotional virions just can’t deal with rejection – that and our cells just aren’t as smart as we need them to be. I’m not sure if you are a Trekkie; however, it reminds me of the Borg and The Enterprise’s encounter – The Enterprise adapting to The Borg’s every frequency of their phasers, bypassing their bruteforce.

That does make sense that our cells do need that protein surface for energy; however, I never thought it would actually be the surface itself. Interesting.

I did read about that somewhere – because of the Bubonic Plague causing some genetic mutation, if I’m not mistaken.

To which I responded:

Virus particles are not alive – but once they infect a living cell they can evolve.

Both cells and viruses are smart – they both have managed to be around for a long time. We have great immune systems; virus infected cells can evolve very quickly. It’s an arms race.

Correct, one idea is that the mutation conferring resistance to HIV was acquired in the Plague, but that’s hard to prove.

The mutation we are discussing is of course ccr5delta32, which confers resistance to infection with HIV-1 (the illustration shows the HIV-1 glycoprotein binding CD4 and ccr, a chemokine receptor). You can read more about ccr5delta32 here or listen to us discuss it on TWiV #278. We also talked about virus-receptor arms races on TWiV #242, and I wrote about it here.

TWiV 276: Ramblers go viral

On episode #276 of the science show This Week in Virology, Vincent meets up with Susan Baker and Tom Gallagher at Loyola University to talk about their work on coronaviruses.

You can find TWiV #276 at www.microbe.tv/twiv.

TWiV 226: Taking the viral A train with Terry Dermody

On episode #226 of the science show This Week in Virology, Vincent and Dickson speak with Terry Dermody about his career in medicine and virology.

You can find TWiV #226 at www.microbe.tv/twiv.

TWiV 215: Illuminating rabies and unwrapping a SARI

On episode #215 of the science show This Week in Virology, Vincent, Alan, and Kathy review the finding that rabies virus infection alters but does not kill neurons, and provide an update on the novel coronavirus in the Middle East.

You can find TWiV #215 at www.microbe.tv/twiv.

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

TWiV 201: Bond, covalent bond

On episode #210 of the science show This Week in Virology, the complete TWiV team reviews identification of the cell receptor for hepatitis B and D viruses, and the cell enzyme that cleaves the genome-linked protein from picornaviral RNA.

You can find TWiV #210 at www.microbe.tv/twiv.

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.