Giving your neighbor the gift of virus susceptibility

SiphoviridaeVirus infections initiate when virions bind to receptors on the cell surface. It is well known that cells can be made susceptible to infection by providing DNA encoding the virus receptor. For example, mice cannot be infected with poliovirus, but become susceptible if they are given the human poliovirus receptor gene. Now we have learned that providing the receptor protein is sufficient to make cells susceptible to infection (link to paper).

Bacteriophages determine the composition of microbial populations by killing some bacteria and sparing others. Bacteriophages are typically host specific, a property that is largely determined at the level of attachment to host cell receptors. How resistant and sensitive bacteria in mixed communities respond to phage infection has not been well studied.

Several phages (including SPP1, pictured) of the soil bacterium Bacillus subtilis first attach to poly-glycosylated teichoic acids (gTA), and then to the membrane protein YueB, leading to injection of DNA into the cell. Cells that lack the gene encoding either of these proteins are resistant to infection.

When a mixed culture of resistant and susceptible B. subtilis cells were infected with phage SPP1, both types of cells became infected and killed. Infection of resistant cells depended on the presence of susceptible cells, because no infection occurred in pure cultures of resistant cells.

Both infected and uninfected bacteria release small membrane vesicles that contain proteins, nucleic acids, and other molecules. Phage SPP1 can attach to  membrane vesicles released by susceptible strains of B. subtilis, showing that they contain viral receptor proteins. Furthermore, phage SPP1 can infect resistant cells that have been incubated with membrane vesicles from a susceptible strain – in the absence of intact susceptible cells.

These results show that membrane vesicles released by susceptible bacteria contain viral receptors that can be inserted into the membrane of a resistant cell, allowing infection. Because phage infection can lead to transfer of host DNA from one cell to another, the results have implications for the movement of genes for antibiotic resistance or virulence. It’s possible that such genes may move into bacteria that have only ‘temporarily’ received virus receptors via membrane vesicle transfer.

These findings should also be considered when designing phage therapy for infectious diseases. The idea is to utilize phages that are host specific and can only destroy the disease-producing bacteria. It’s possible that the host range of such phages could be expanded by receptor protein transfer. As a consequence, unwanted genes might make their way into ‘resistant’ bacteria.

I wonder if membrane vesicle mediated transfer of receptors also occurs in eukaryotic cells. They shed membrane vesicles called exosomes, which contain protein and RNA that are delivered to other cells. If exosomes bear receptors for viruses, they might be able to deliver the receptors to cells that would not normally be infected. The types of cells infected by a virus would thereby be expanded, potentially affecting the outcome of viral disease.

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, 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

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

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

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

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