TWiV 175: More than one way to skin a virus

March 18, 2012

microneedleHosts: Vincent RacanielloAlan Dove, and Matt Frieman

Vincent, Alan, and Matt discuss herpes simplex encephalitis in children with innate immune deficiency, and the local response to microneedle-based influenza skin immunization.

Click the arrow above to play, or right-click to download TWiV 175 (57 MB .mp3, 80 minutes).

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Weekly Science Picks

MattPhage and the Origins of Molecular Biology
AlanDigital Imagine Institute
Vincent – iPad apps Goodreader and Notability

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JaneSmoking Ears and Screaming Teeth by Trevor Norton

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13 comments on “TWiV 175: More than one way to skin a virus

  1. Junio C Hamano Mar 19, 2012

    If only certain types of cells are susceptive to a virus, and if the cells around skin are not, I wonder if MN vaccination can safely be done with vaccine not based on a killed or attenuated virus, but a live virus.

    Is that a crazy thought?

    • Matt Frieman Mar 19, 2012

      I think that even if a virus cant infect a skin cell, it will be taken up by macrophage like cells in the skin, so it will definately be presented to the lymphoid tissue nearby.  But even if the virus doesnt replicate in those cells you would worry about giving a completely live virus to the skin because it could be easily spread to other parts of your body by touch, ex. rubbing your eyes, so mucus membranes could be infected by the virus, cuts on your hand or arm could allow the virus deeper, etc.  So I think that using purified protein or killed virus in this context is safer.  


    • Good question. As Matt says it should be properly presented to the immune system, it’s just a matter of whether it would still be attenuated. For example, the attenuated poliovirus vaccines don’t (generally) cause paralysis when you ingest them, but I could imagine that when injected into the skin they might behave differently. And the shedding issue that Matt refers to is real – one of the smallpox vaccines is infectious, and there are cases of rash being spread to others who have contact with the vaccinee. We have talked about these cases on TWiV.

  2. EllenHunt Mar 19, 2012

    Qdots are nice, but they have significant limitations. Their primary limitation is, I think a quality control problem. Qdots, in practice, show wide emission width, which means that there is broad overlap in fluorescence wavelength even when the emission peaks are widely separated.

    What this means is that while it is useful for gross multi-color imagery, you can’t use it for things like confocal microscopy because everything lights up. That is too bad, because Qdots would be very helpful in confocal microscopy because it is common (particularly for beginners, but its also a problem for experienced people) to photobleach before getting a good image. Qdots don’t photobleach, and for this reason I looked into them.

    If the makers of Qdots could deliver  emission spectra as narrow as chemical fluorophores, it would be a big help.  I can tell them at least one way they could manage it, and that is to run their Qdots through flow cytometry sorters that had extremely narrow bandgap filters. If they started doing this, they might begin to get a handle on their manufacturing processes.

    • Matt Frieman Mar 19, 2012

      Hi Ellen,

      I would bet that they are working on this type of chemistry right now, since the Qdot idea is taking off.  They need to be so bright for the in vivo imaging, but that brightness is overkill for confocal.  So there must be a happy medium.  I would be some company is working on this right now.


  3. Interesting podcast thanks. 

  4. Matt Frieman Mar 19, 2012

    Most of the Phage book is online free on Google Books.  My favorite chapter is about discovering how to plaque phage.  Very cool old school science stuff by Renato Dulbecco.

  5. I’m not sure how good this way of vaccinating would be for all kinds of viruses, especially ones that need protection at specific sites, like the upper respiratory tract, gut mucosa or genital tract. My thought was that the microneedles biased toward systemic immunity and this is sufficient for protection against flu – I think. You can tailor the protection with specifically inducing the response in certain tissues like using aerosolised vaccine in the lungs. 

  6. ARumm Mar 21, 2012

    Dear Vinnie and the Twivettes,

    In TWiV 175, Tessa had written in asking about services for recording notes and storing PDFs, and there was some talk about general notetaking software as well as services for compiling references and annotation software. I just wanted to let you all know about Evernote, which is the software I personally use.

    Evernote has a lot of different ways to access it. It has a web interface, as well as binaries for Mac and PC. It also has Android, iOS, Blackberry, and WebOS for cell phones, as well as plugins for Chrome, Firefox, and Safari. You can also e-mail notes directly to Evernote, if you somehow had access to a device that can e-mail that doesn’t have an app. This was important for me, because I had just switched to an Android telephone, but have a Blackberry tablet, a desktop, a laptop, and also wanted to access the software from PCs in the lab.

    My primary use for Evernote is not for recording notes on PDFs (I’ve not been reading as many articles as I used to since I graduated; something I need to fix). But its effectiveness in other realms is excellent. I keep todo lists and daily logs on there that I can update or check from my laptop, desktop or from my phone. When I take notes by hand, as long as I have my phone with me I’m set. I’ll write/draw whatever I need in my sketchbook or a notebook or a barnapkin, take a picture of the page with my cellphone, and directly upload it to my evernote. Uploaded pictures are gradually analysed, searching for text (even handwritten), so that you can actually search for things in your pictures (aka notes you take on paper). If you have an ipad, I think there’s a straight-to-handwriting option in there as well.

    The cons are as follows: to my knowledge, there is no ability to insert notes directly into PDFs. The free version has a maximum monthly upload of 50MB (all of the notes/pictures/pdfs you upload to it are stored in the cloud). PDFs are not searchable in the free version either, although they are in the paid version which costs $5/month. You can upload a PDF to a note, however, and then record whatever notes you wanted to about that.

    The last time I used it to take notes on an article, what I did was make a note with the article in it (to make sure I always had access to the PDF), then copy and pasted any quotes from the article I needed and typed my own notes as well. Evernote also has an API which means that people can develop software designed to interface with it. Hopefully somebody out there will make a plug-in that lets you make annotations to PDFs directly.

    I know this letter is too long to read on the air, but I recommend taking a look at Evernote simply because of it’s broad usefulness. I myself was very excited to find the program, because I was able to condense several different things I needed into one universally accessible workflow; notes I took, to-do lists, reminders, reading, and daily logs were all spread across google docs, thumb drives, crumpled receipts in the console of my car, and real-world physical hard copy notebooks (how Twentieth Century). I’m sure some listeners may be able to benefit from the service.

    Thanks again for the amazing Podcast; I look forward to it every week!

    • Thanks, ARumm. We are recording TWiV today and we’ll link to this. Love the salutation!

    • Matt Frieman Mar 22, 2012


      I personally use Evernote as well for taking notes in seminars and lists for lab, etc.  I found that typing on the iPad in a lecture was much easier than using a stylus (I have the Jot).  I would love a program that works better with handwriting recognition but I havnt found one yet.  It is also free and syncs from ipad to desktop to iPhone automatically, so it can be accessed from everywhere.

      The other cute thing it does is if you are on a Mac (not sure if it works on PC too this way) and have an appointment set in iCal for say “Racaniello Seminar”, when you start a new Evernote file near the time of the seminar, it automatically calls it “Racaniello Seminar Notes” in the file name.  A pretty cute and intuitive connection between programs.



  7. Shane Carlson Mar 28, 2012

    In your latest TWIV (#175) the subject of CFS (ME) and genetic predisposition arose.  I would suggest a quick search of Pubmed using the keywords ‘CFS,’ ‘genetic,’ and ‘predisposition.’  You’ll find close to 30 relevant articles.

    Amongst the more recent articles, one by a group in Utah utilizing the extensive genealogical records available there stands out for it’s focus on heritability rather than gene expression. 

    “Evidence for a heritable predisposition to Chronic Fatigue Syndrome” ( by Albright et al
    “observed significant excess relatedness of CFS cases compared to that
    expected in this population. Significant excess relatedness was observed
    for both close (p <0.001) and distant relationships (p = 0.010). [They]
    also observed significant excess CFS relative risk among first (2.70,
    95% CI: 1.56-4.66), second (2.34, 95% CI: 1.31-4.19), and third degree
    relatives (1.93, 95% CI: 1.21-3.07).

    In conclusion the authors wrote: "These analyses provide strong support for a heritable contribution to predisposition to Chronic Fatigue Syndrome."

    Contrary to Alan Dove's assertion that environment was a likely explanation for findings of familial association in CFS, the RR in this study for third degree relatives (1.93) suggests that genetic heritability is a more likely explanation in familial CFS.

    From the study's Conclusion:

    The existence of a Utah resource
    combining up to 15 generations of genealogy data with medical diagnosis
    data from 1993 has allowed testing of the hypothesis of a heritable
    contribution to CFS. The methods used in this study have previously
    provided evidence for a heritable component to many diseases, including:
    prostate cancer, influenza mortality, aneurysm, cancer, rotator cuff
    disease, asthma mortality, and diabetes, among others [28,32-34].
    Studies of Utah high-risk pedigrees identified in the UPDB have lead to
    the discovery of multiple cancer predisposition genes including BRCA1, BRCA2, p16, and HPC2/ELAC2 [35-38].
    The UPDB data analyzed represents a homogeneous population that has
    been shown to be genetically representative of Northern Europe, with
    normal U.S. inbreeding levels [39,40].
    increased risks among first degree relatives are often referred to as
    providing evidence for a "genetic" contribution to disease. However,
    given the sharing among close relatives of their genes, lifestyle, and
    environment, increased first degree risk may simply indicate familial
    clustering, it does not provide evidence for a genetic contribution.
    However, significant excess risks in second and third degree relatives
    strongly indicates a genetic contribution to disease, given the much
    lower likelihood of these relatives sharing common risks and

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