TWiV 285: Hokies go viral

On episode #285 of the science show This Week in Virology, Vincent meets up with XJ Meng and Sarah McDonald at Virginia Tech to talk about their work on viruses of swine and rotaviruses.

You can find TWiV #285 at www.microbe.tv/twiv.

TWiV 86: Dark matter with Dr. Eric Delwart

Hosts: Vincent Racaniello, Rich Condit, and Eric Delwart

In episode #86 of the podcast This Week in Virology, Vincent and Rich travel to the Blood Systems Research Institute in San Francisco to speak with Eric Delwart about his work on virus discovery.

This episode is sponsored by Data Robotics Inc. Use the promotion code TWIVPOD to receive $75-$500 off a Drobo.

To enter a drawing to receive 50% off the manufacturers suggested retail price of a Drobo S or FS at drobostore.com, fill out the questionnaire here.

Click the arrow above to play, or right-click to download TWiV #86 (59 MB .mp3, 81 minutes)

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Links for this episode:

Weekly Science Picks

Rich – Google Crisis Response – Gulf of Mexico Oil Spill
Vincent
HHMI resources for teachers and students (thanks, Jim!)
EricVaccine by Arthur Allen

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FDA clears rotavirus vaccines

The US Food and Drug Administration has updated its recommendations on both Rotarix and RotaTeq, vaccines for the prevention of rotavirus disease in infants:

Based on careful evaluation of a variety of scientific information, FDA has determined it is appropriate for clinicians and health care professionals to resume the use of Rotarix and to continue the use of RotaTeq.

In making its recommendation, the FDA considered the strong safety records of both vaccines, including clinical trials in tens of thousands of individuals and the use of the vaccines in millions of recipients. There is no evidence that either porcine circovirus type 1 or type 2 poses a safety risk to humans, and neither virus is known to infect humans or cause disease.

The FDA also noted that the benefits of the rotavirus vaccines are considerable and outweigh the small theoretical risk of the viral contaminant.

The product labels will be updated to reflect the fact that the vaccine contains a PCV contaminant. In addition, GlaxoSmithKline will rederive Rotarix so that it does not contain PCV. Merck has not yet made a decision about whether they should produce a PCV-free rotavirus vaccine. But if my suggestion carries any weight at Merck (I know it does not), they should not hesitate to follow GlaxoSmithKline’s lead.

Porcine circovirus DNA found in RotaTeq

The US Food and Drug Administration recently recommended that administration of Glaxo SmithKline’s Rotarix vaccine, which protects against rotavirus infection, be suspended after an independent research group found that the vaccine contains DNA of porcine circovirus type 1. Now the FDA reports finding circovirus DNA in the rotavirus vaccine made by Merck:

FDA recently received information from Merck & Co, Inc. that its preliminary studies have identified fragments of DNA from PCV1 and from a related porcine circovirus type 2 (PCV2) in its RotaTeq vaccine. Merck’s findings suggest that the number of PCV DNA fragments in its vaccine may be smaller than what has been found in Rotarix.

FDA has so far not recommended suspension of RotaTeq use. The Vaccines and Related Biological Products Advisory Committee meets today, after which FDA will make further recommendations on the use of the licensed rotavirus vaccines in the United States.

The source of porcine circovirus type 1 DNA in both Rotarix and RotaTeq is likely to be trypsin used during propagation of the cell cultures necessary for vaccine production. The enzyme is produced from porcine pancreas.

Update 10 May 2010: The FDA has posted a briefing document for the VRBPAC meeting that was held this past Friday. The Los Angeles Times reports on the outcome of the meeting:

Members of a Food and Drug Administration advisory committee meeting Friday urged physicians to continue using both commercial rotavirus vaccines despite evidence that both carry trace contaminants from a harmless pig virus. The panel did not take a formal vote on a recommendation, but a majority of participants said they thought the benefits of the vaccine far outweigh any potential risk. An agency spokeswoman said it would make no immediate recommendation on the vaccines, but would act expeditiously to come to a decision.

Finally, there are some good quotations from committee members in the article at Medscape Today.

Virology lecture #17: Acute infections


Download: .wmv (322 MB) | .mp4 (91 MB)

Visit the virology W3310 home page for a complete list of course resources.

TWiV 77: Non-nuclear proliferation

Hosts: Vincent Racaniello, Alan Dove, and Rich Condit

Vincent, Alan, and Rich revisit circovirus contamination of Rotarix, then discuss poxvirus-like replication of mimivirus in the cell cytoplasm, and whether seasonal influenza immunization increases the risk of infection with the 2009 H1N1 pandemic virus.

This episode is sponsored by Data Robotics Inc. Use the promotion code TWIVPOD to receive $50 off a Drobo or $100 off a Drobo S.

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Click the arrow above to play, or right-click to download TWiV #77 (60 MB .mp3, 83 minutes)

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Weekly Science Picks

Rich The Way We Work by David Macaulay
Alan DimDim
Vincent Polio: An American Story by David Oshinsky

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Is circovirus DNA infectious?

Circovirus genomeThe US Food and Drug Administration does not want Rotarix, the rotavirus vaccine, to be used because it contains porcine circovirus 1 DNA. If complete copies of the circovirus genome were present, would they constitute a potential threat to recipients? Put another way, is circovirus DNA infectious?

Here is the information you need to answer this question.

  • The circovirus genome is a circular, single stranded DNA molecule (pictured).
  • To infect a cell, the two viral proteins encoded in the DNA must be produced.
  • To produce proteins, mRNA must be synthesized from the viral DNA.
  • Single-stranded DNA cannot be copied  into mRNA; the DNA must be double-stranded.
  • The circovirus particle consists of a protein shell surrounding the viral DNA. There are no other components in the virion.
  • During infection of cells by circoviruses, the particles enter the nucleus where the viral DNA is released
  • If naked DNA is added to cells, a good fraction ends up in the nucleus.

Knowing these facts, can you determine whether introduction of circovirus DNA into cells would lead to viral replication?

Porcine circovirus DNA in rotavirus vaccine

Circovirus_genomeThe US Food and Drug Administration has recommended that administration of the Rotarix vaccine, which protects against rotavirus infection, be suspended. This action comes after an independent research group found that the vaccine contains DNA of porcine circovirus type 1.

Rotaviruses are the single leading cause of diarrhea in infants and young children. Each year rotavirus gastroenteritis causes over 1,250,000 episodes of diarrhea and 527,000 deaths, mainly in developing countries. Rotavirus vaccines are used to reduce the global burden of rotavirus disease. Rotarix, the vaccine manufactured by GlaxoSmithKline, is an infectious, attenuated vaccine that is administered orally to infants.

The genetic information of rotaviruses consists of 11 segments of double-stranded RNA. In contrast, porcine circoviruses are small viruses with a circular, single stranded DNA genome (pictured). At 1.7 kb in length, the DNA is among the smallest known viral genomes and encodes only two proteins. Porcine circovirus 1 was originally discovered as a contaminant of a pig kidney cell line. Later a second strain, porcine circovirus 2, was isolated and shown to be associated with postweaning multisystemic wasting disease, an emerging disease of swine.

Porcine circovirus 1 DNA was also found in the cells used to produce Rotarix. Therefore the contaminant has been present since the early days of vaccine development, including clinical trials. A different rotavirus vaccine produced by Merck, called RotaTeq, does not contain porcine circovirus DNA.

It’s not at all clear that the presence of porcine circovirus 1 DNA in Rotarix is a problem. Circoviruses have not been associated with human disease, and porcine circovirus 1 has not been found to cause disease in any animal. Many humans have antibodies to these viruses, including porcine circovirus, indicating that they were infected at one time. Furthermore, it’s not known if the vaccine contains infectious virus or DNA fragments. Nevertheless, it’s always preferable to err on the side of caution, as the FDA has done.

Because porcine circoviruses are widespread in commercial swine populations, there have been concerns about the use of porcine organs for xenotransplantation and for the production of products used in humans such as factor VIII, heparin, insulin and pepsin. It is therefore important to ensure that such products do not contain infectious circoviruses.

This incident will undoubtedly further increase public distrust of vaccines and vaccine manufacturers. I have not yet seen the journal article describing these findings, so I can’t comment on why the contaminant was not identified early in vaccine development. According to the FDA, “In four to six weeks, FDA will convene an expert advisory committee and make additional recommendations on the use of rotavirus vaccines.” If Rotarix is found to contain infectious porcine circovirus, then its use will certainly be discontinued. However, detection of small noninfectious fragments of porcine circovirus DNA Rotarix will likely lead to resumption of vaccine use. In either case, new lots of vaccine should be produced using circovirus-free cells.

Tischer I, Bode L, Apodaca J, Timm H, Peters D, Rasch R, Pociuli S, & Gerike E (1995). Presence of antibodies reacting with porcine circovirus in sera of humans, mice, and cattle. Archives of virology, 140 (8), 1427-39 PMID: 7544971

Fenaux M, Opriessnig T, Halbur PG, Xu Y, Potts B, & Meng XJ (2004). Detection and in vitro and in vivo characterization of porcine circovirus DNA from a porcine-derived commercial pepsin product. The Journal of general virology, 85 (Pt 11), 3377-82 PMID: 15483254

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)

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Links for this episode:

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

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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

TWiV 51: ALVAC-HIV and AIDSVAX B/E

twiv-200Hosts: Vincent Racaniello, Dick Despommier, and Alan Dove

On episode #52 of the podcast “This Week in Virology”, Vincent, Dick, and Alan (with a cameo appearance by Rich Condit) review the world’s largest Phase III study of a complex HIV vaccine candidate in Thailand, immunization of salmon against infectious salmon anemia virus, and an outbreak of blueberry shock virus in Michigan.

Click the arrow above to play, or right-click to download TWiV #51 (60 MB .mp3, 84 minutes)

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Links for this episode:
HIV vaccine shows promise for the first time – description of the program, FDA background document (pdf), NEJM review on why AIDS vaccine is difficult (pdf), and arguments for the trial
Chile immunizes salmon (USGS article on the virus, pdf)
Blueberry virus strikes Michigan research center (information on the disease and the virus)
Rotavirus seasonality (thanks Didier!)
Viruses and the tree of life at virology blog
Big brains have evolved twice (thanks Arsen!)

Weekly Science Picks
Alan Bat Rabies and Other Lyssavirus Infections
Dick Boosting Vaccines: The Power of Adjuvants (Scientific American; subscription required)
Vincent The Ig Nobel Prizes by Marc Abrahams

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 tagging them with to:twivpodcast.