TWiV 477: Raiders of the lost Arc

The TWiVodrome explains how a gag-like protein from a retrotransposon forms virus-like particles that carry mRNA within vesicles across the synapse.

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TWiV 459: Polio turns over a new leaf

The TWiV team reviews the first FDA approved gene therapy, accidental exposure to poliovirus type 2 in a manufacturing plant, and production of a candidate poliovirus vaccine in plants.

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TWiV 372: Latent viral tendencies

TWiVOn episode #372 of the science show This Week in Virology, the TWiV-osphere introduces influenza D virus, virus-like particles encoded in the wasp genome which protect its eggs from caterpillar immunity, and a cytomegalovirus protein which counters a host restriction protein that prevents establishment of latency.

You can find TWiV #372 at

TWiV #170: From variolous effluvia to VLPs


On This Week in Virology #170, hosts Alan, Rich, and Dickson discuss Edward Jenner’s paper on cowpox vaccine, then move 200 years later to modern vaccines against norovirus, influenza H5N1, and more.

You can find TWiV #170 at

TWiV 129: We’ve got mail

rich unwindsHosts: Vincent Racaniello, Alan Dove, Dickson Despommier, and Rich Condit

Vincent, Alan, Dickson and Rich answer listener questions about XMRV, yellow fever vaccine, virus-like particles, West Nile virus, amyotrophic lateral sclerosis and human endogenous retroviruses, multiplicity of infection, and how to make a poxvirus.

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Weekly Science Picks

Rich – Polyxeni Potter and EID covers
Dickson – American Museum of Natural History
Alan –
Moon Trees (EurekAlert! article)
Vincent – Infection Landscapes

Listener Picks of the Week

Didier  – The Vaccines (MySpace)
/Sven-Urban –
The Science of Discworld by Terry Pratchett
GarrenOmega Tau podcast

Send your virology questions and comments (email or mp3 file) to, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at and tag them with twiv.

TWiV 47: Vertical vaccine farm

twiv-200Hosts: Vincent Racaniello and Dick Despommier

On episode #47 of the podcast “This Week in Virology”, Vincent and Dick discuss influenza virus-like particle vaccines produced in insect and plant cells, rapid sharing of influenza research, and answer listener questions about cytomegalovirus, viral evolution and symbiosis and much more.

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Links for this episode:
A Farm on Every Floor
Influenza virus-like particles in insect and plant cells
PLoS Currents: Influenza
Transmission of 2009 H1N1 influenza virus to turkeys [Thanks Debbie!]
Baxter produces Vero cell H1N1 vaccine [Thanks Peter!]
Boundaries of Darwinism podcast [Thanks David!]
Phages in human intestine: papers onetwothree [Thanks Terry!]
Post-exposure varicella vaccine [Thanks Patricia!]
Open science movement hereherehere, and here [Thanks Jim!]
Graduate programs in virology [Thanks Greggory and Blake!]
Post-exposure Marburg and Ebola vaccines [Thanks John!]
Vaccinia infection in the laboratory [Thanks Russ!]
Animations of bacteriophage T4 life cycle [Thanks Jim!]

Weekly Science Picks
Vincent Bionumbers
Dick Ocean: An Illustrated Atlas by Sylvia A. Earle, Linda K. Glover

Send your virology questions and comments (email or mp3 file) to or leave voicemail at Skype: twivpodcast

Influenza virus-like particle vaccine

influenza-vlpA new type of vaccine against influenza, made with virus-like particles, has been shown to protect ferrets from infection with the 2009 H1N1 swine-origin strain. What is a virus-like particle, and how is it produced?

If you have been taking influenza 101, you know that new virus particles are produced in infected cells by budding. During this process, the membrane bulges from the cell and is eventually pinched off to form a free particle. These virus particles contain the viral RNA segments, and an assortment of viral proteins including PA, PB1, PB2, NP, M1, M2, HA, and NA. But not all of those viral proteins are needed to produce an influenza virus particle. When only the viral HA, NA, and M1 proteins are synthesized in cells, particles are released from cells that look very much like influenza virions (illustrated). These are called ‘virus-like particles’ because they resemble influenza viruses, but lack the viral genome and many viral proteins.

Influenza virus-like particles are not infectious, but they are immunogenic: when injected into animals, they induce the production of anti-viral antibodies that can block infection. In one study, virus-like particles were produced in cultured insect cells by using an insect virus vector – a baculovirus – to deliver genes encoding the influenza HA, NA, and M1 proteins. Mice inoculated with these virus-like particles were protected after challenge with infectious virus. More recently, mice vaccinated with virus-like particles produced with proteins from an H5N1 avian strain were protected against challenge with lethal H5N1 viruses.

These findings suggest that virus-like particles could be used in humans to protect against influenza infection. They offer a number of advantages over the current influenza virus vaccines, most of which are prepared by growing virus in embryonated chicken eggs. Viral infectivity is destroyed with formalin, and the virions are then disrupted with detergents. Virus-like particle vaccines would not require these treatments, and would be available to individuals with egg allergies. Some influenza virus vaccines are produced in cell culture, but these are also treated to eliminate infectivity.

Another important advantage of the virus-like particle vaccine is that it can be produced relatively rapidly: within weeks, compared to months for egg-produced vaccines. This property would be especially useful when new pandemic strains emerge. For example, the swine-origin H1N1 influenza virus emerged in the spring of 2009, and vaccine manufacturers are scrambling to have a product ready for the fall.

Because an influenza virus-like particle vaccine is a new type of vaccine, many years of testing in animals and in humans will be required before it can be used. Some of the questions that must be addressed include the safety of the vaccine in humans, whether the anti-viral antibody repertoire induced by the vaccine is sufficiently broad, and of course whether immunization confers efficient protection against challenge in the majority of recipients.

I am particularly curious about how an influenza virus-like particle vaccine would compare with the infectious, attenuated influenza vaccine, Flumist. This intranasally-administered vaccine mimics a natural infection and has been shown to be more effective in preventing influenza than inactivated vaccine. While virus-like particle vaccines are an attractive option, they are not infectious and therefore might not induce the same antibody repertoire as would an infectious virus. A disadvantage of Flumist is that it is produced in eggs. If influenza virus-like particles prove safe and efficacious in humans, they could replace the egg-grown, inactivated vaccines.

Pushko, P., Tumpey, T., Bu, F., Knell, J., Robinson, R., & Smith, G. (2005). Influenza virus-like particles comprised of the HA, NA, and M1 proteins of H9N2 influenza virus induce protective immune responses in BALB/c mice Vaccine, 23 (50), 5751-5759 DOI: 10.1016/j.vaccine.2005.07.098

Bright, R., Carter, D., Crevar, C., Toapanta, F., Steckbeck, J., Cole, K., Kumar, N., Pushko, P., Smith, G., Tumpey, T., & Ross, T. (2008). Cross-Clade Protective Immune Responses to Influenza Viruses with H5N1 HA and NA Elicited by an Influenza Virus-Like Particle PLoS ONE, 3 (1) DOI: 10.1371/journal.pone.0001501

Virology pop quiz: Answers

BaculovirusA few weeks ago I asked readers to find the errors in the following statement concerning an experimental influenza vaccine produced by Protein Sciences which involves synthesis of the viral HA protein in insect cells.

They warned that the virus could mutate during the southern hemisphere’s flu season before returning north in a more lethal form in autumn, in a pattern similar to that seen in the deadly 1918 flu pandemic, which claimed an estimated 20 to 50 million lives around the globe.

The CDC (Centers for Disease Control and Prevention) sent us a dead virus, which is perfectly safe, and then we extracted genetic information from that virus.

The statement ‘in a pattern similar to that seen in the deadly 1918 flu pandemic’ is wrong. There is no evidence that mutation led to the emergence of a ‘more virulent’ virus that caused more severe disease in the fall of 1918. The only virus available to study was reconstructed from material obtained in November 1918. The first influenza virus was not isolated until 1933. The idea that a more virulent virus emerged in the fall has nevertheless become firmly established – without any scientific evidence to support the hypothesis. See “Riding the influenza pandemic wave” for more information.

The second problem is the statement that CDC sent the company a dead virus. Viruses are not living, so they cannot be killed. What the company received is an inactivated virus which cannot replicate in cells. There are many ways to inactivate viral infectivity, including heat, ultraviolet radiation, or treatment with chemicals such as formalin.

For extra credit I asked readers to critique the following statement:

Protein Sciences’ technology is also safer “because these caterpillars don’t have any association with man or other animals, so there’s no chance for their cells to learn how to propagate human viruses,” Adams told AFP.

What exactly was the spokesman trying to say? That there is no chance that influenza virus will replicate in insect cells? That’s impossible to say. The fact that ‘caterpillars don’t have any association with man’ is irrelevant (I’m not an entomologist, but I don’t believe that statement is correct). It’s possible that the virus could be adapted to grow in insect cells in the laboratory. And of course, cells don’t ‘learn’ how to propagate viruses. When viruses are selected for growth in new cells – a process that we call expanding the tropism of the virus – changes in the viral genome are usually responsible.

Parenthetically, there is a better way to make an influenza virus vaccine in insect cells – by synthesizing virus-like particles. When the influenza viral HA, NA, and M1 proteins are made in insect cells, virus-like particles are produced that lack the viral genome. These have been shown to be immunogenic in ferrets, and are capable of inducing a protective immune response.

Ross, T., Mahmood, K., Crevar, C., Schneider-Ohrum, K., Heaton, P., & Bright, R. (2009). A Trivalent Virus-Like Particle Vaccine Elicits Protective Immune Responses against Seasonal Influenza Strains in Mice and Ferrets PLoS ONE, 4 (6) DOI: 10.1371/journal.pone.0006032

TWiV 42: Bats and ticks

twiv-200Hosts: Vincent Racaniello, Dick DespommierAlan Dove, and Delthia Ricks

In episode #42 of the podcast “This Week in Virology”, Vincent, Dick, Alan, and Delthia Ricks discuss a new influenza virus-like particle vaccine, dog flu, ultrasensitive pen-sized virus detector, imported rabies in the US, Crimean-Congo hemorrhagic fever, and next season’s flu vaccines.

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Links for this episode:
Trivalent virus-like particle vaccine
Canine flu virus vaccine
Ultrasensitive virus detector
Rabies imported into the US
Crimean-Congo hemorrhagic fever in Kazakhstan
FDA approves seasonal flu vaccine for fall
Yields of 2009 H1N1 vaccine are low
FDA may fast-track approval of 2009 H1N1 vaccine

Weekly Science Picks
Delthia 100 questions and answers about influenza by Delthia Ricks
Vincent Effect Measure

Send your virology questions and comments (email or mp3 file) to or leave voicemail at Skype: twivpodcast