TWiV 330: A swinging gate

On episode #330 of the science show This Week in Virology, the TWiVers explain how a protein platform assists the hepatitis C virus RNA polymerase to begin the task of making viral genomes.

You can find TWiV #330 at www.microbe.tv/twiv.

TWiV 328: Lariat tricks in 3D

On episode #328 of the science show This Week in Virology, the TWiVocateurs discuss how the RNA polymerase of enteroviruses binds a component of the splicing machinery and inhibits mRNA processing.

You can find TWiV #328 at www.microbe.tv/twiv.

Treatment of Ebola virus infection with brincidofovir

brincidofovirThe Liberian man who was diagnosed with Ebola virus infection after traveling to Dallas, Texas, was treated with an antiviral drug called brincidofovir. This drug had originally been developed to treat infections with DNA-containing viruses. Why was it used to treat an Ebola virus infection?

Brincidofovir (illustrated) is a modified version of an antiviral drug called cidofovir, which inhibits replication of a variety of DNA viruses including poxviruses and herpesviruses. When cidofovir enters a cell, two phosphates are added to the compound by a cellular enzyme, producing cidofovir diphosphate. Cidofovir is used by viral DNA polymerases because it looks very much like a normal building block of DNA, cytidine. For reasons that are not known, incorporation of phosphorylated cidofovir causes inefficient viral DNA synthesis. As a result, viral replication is inhibited.

Cidofovir was modified by the addition of a lipid chain to produce brincidofovir. This compound (pictured) is more potent, can be given orally, and does not have kidney toxicity, a problem with cidofovir. When brincidofovir enters a cell, the lipid is removed, giving rise to cidofovir. Brincidofovir inhibits poxviruses, herpesviruses, and adenoviruses, and has been tested in phase 2 and 3 clinical trials. The antiviral drug is being stockpiled by the US for use in the event of a bioterrorism attack with smallpox virus.

Ebola virus is an RNA virus, so why was brincidofovir used to treat the Dallas patient? According to the drug’s manufacturer, Chimerix,  with the onset of the Ebola virus outbreak in early 2014, the company provided brincidofovir, and other compounds, to the CDC and NIH to determine if they could inhibit virus replication. Apparently brincidofovir was found to be a potent inhibitor of Ebola virus replication in cell culture. Based on this finding, and the fact that the compound had been tested for safety in humans, the US FDA authorized its emergency use in the Dallas patient.

Unfortunately the Dallas patient passed away on 8 October. Even if he had survived, we would not have known if the compound had any effect. Furthermore, the drug is not without side effects and these might not be tolerated in Ebola virus-infected patients. It seems likely that the drug will also be used if other individuals in the US are infected.

Looking at the compound, one could not predict that it would inhibit Ebola virus, which has an RNA genome. RNA polymerases use different substrates than DNA polymerases – NTPs versus dNTPs. NTPs have two hydroxyls on the ribose sugar, while dNTPs have just one (pictured). The ribose is not present in cidofovir, although several hydroxyls are available for chain extension. I suspect that the company was simply taking a chance on whether any of its antiviral compounds in development, which had gone through clinical trials, would be effective. This procedure is standard in emergency situations, and might financially benefit the company.

Update: The NBC news cameraman is being treated with brincidofovir in Nebraska.

TWiV 299: Rocky Mountain virology

On episode #299 of the science show This Week in VirologyVincent visits the Rocky Mountain Laboratories in Hamilton, Montana and speaks with Marshall Bloom, Sonja Best, and Byron Caughey about their work on tick-born flaviviruses, innate immunity, and prion diseases.

You can find TWiV #299 at www.microbe.tv/twiv.

TWiV 148: Retreating into Harvard virology

harvard virology retreatHosts: Vincent Racaniello, Philip Kranzusch, David Knipe, and Priscilla Yang

Vincent, Philip, David, and Priscilla recorded this episode before an audience at the Harvard Virology Program Annual Retreat, where they discussed negative strand RNA viruses, a vaccine against herpes simplex virus type 2, lipidomics of viral infection, and science communication.

The Keynote Speaker at the Harvard Virology retreat is usually an individual, but this year the honor went to TWiV as an example of science communication to the public. Many thanks to members of the Virology Program for a terrific retreat!

Artwork by Silvia Piccinotti, G4

Click the arrow above to play, or right-click to download TWiV 148 (56 MB .mp3, 77 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

Weekly Science Picks

Philip – AntWeb
David –
Herpes-like viruses in corals (PNAS and LiveScience)
Priscilla –
Science museums (Boston, Durham)
Vincent –
Contagion

Listener Pick of the Week

JennyEmerman’s review of Planet of Viruses (PLoS Biology)

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

TWiV 62: Persistence of West Nile virus

The_Persistence_of_MemoryHosts: Vincent Racaniello, Dickson Despommier, and Alan Dove

On episode #62 of the podcast This Week in Virology, Vincent, Dickson, and Alan discuss STEP HIV-1 vaccine failure caused by the adenovirus vector, presence of West Nile virus in kidneys for years after initial infection, adaptation of the influenza viral RNA polymerase for replication in human cells, and the significance of the D225G change in the influenza HA protein.

Click the arrow above to play, or right-click to download TWiV #62 (47 MB .mp3, 66 minutes)

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email.

Links for this episode:

Weekly Science Picks
Dick Smallpox – The Death of a Disease by DA Henderson
Alan Olympus Bioscapes Digital Imaging Competition
Vincent Microbe Magazine

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

TWiV 60: Making viral RNA

TWiV_AA_200Hosts: Vincent Racaniello and Dickson Despommier

Vincent and Dick continue Virology 101 with a discussion of how RNA viruses produce mRNA and replicate their genomes.

Click the arrow above to play, or right-click to download TWiV #60 (51 MB .mp3, 71 minutes)

Subscribe to TWiV in iTunes, by the RSS feed, or by email

Links for this episode:

Weekly Science Picks
Dick The Double Helix by James D. Watson
Vincent
Worms and Germs Blog

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also send articles that you would like us to discuss to delicious and tag them with to:twivpodcast.

Below is a video of TWiV 60, which highlights the diagrams I referred to during the podcast.

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Download TWiV 60 video. These videos are slightly larger (800 x 512) than the flash version shown above

186 MB .mov video file

584 MB .wmv video file