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TWiV 121 Letters

Gopal writes:

Hello, TWiV-ers,

I am a science journalist based in India and have, over time, become addicted to TWiV. I enjoy the jokes and puns that come along, making TWiV a nice way to to broaden my knowledge and keep up to date. (Oh - and I also faithfully listen to TWiP.)

I just read an article in The Scientist about Charlie Rice's work with the Hepatitis C virus (http://www.the-scientist.com/2010/12/1/24/1/ ). The article says:

"Vertex’s protease inhibitor, VX-950 (now known as telaprevir), has emerged as a leading agent for the treatment of HCV patients with the genotype-1 strain of the disease. A second compound, boceprevir, developed by Schering-Plough, proved equally effective in those patients."

I have two questions:

As both drugs in question treat just one genotype, is it the case that there is no conserved region in the protease that can be targeted so that all or most strains of Hepatitis C can be treated? I presume that treatment will be a lot cheaper if a single drug can be used against multiple strains than when different drugs are needed for various strains. The latter might also mean no drugs being developed for strains common in developing countries.

If not, are there any other viral proteins that are being or could be looked at for the same purpose?

Maybe you could consider taking up Hepatitis C as a topic in TWiV and perhaps have Dr. Rice join the discussion.

Regards,

-- Gopal

Jacob writes:

Hi all,

I am a molecular biologist working in Biometrology. I want to say that as someone who can understand much of the technical details, you guys do a very good job of relaying information to audiences from many different educational backgrounds. Also, as an Australian, it is nice to hear us getting a mention quite often, mostly in regards to our rabbits.

I was just listening to TWIV 112 and wanted to add something to Rich's pick of the week (The Scientists top 10 innovations 2010; #1 was third gen seq, eg Pac Bio). The 3rd generation sequencing technology is certainly amazing, but you guys missed one of the most amazing things about it. Someone mentioned about the background of the other nucleotides floating around but the thing with this technology is that the reaction vessel is smaller than the wavelength of light. This prevents the background fluorescence from reaching the detector. It works in a similar way to your microwave oven, in that the microwaves cannot pass through the holes in the door, but visible light can, as its wavelength is smaller. The polymerase is attached to a transparent layer at the bottom of the reaction vessel, so the light from the fluorescently tagged diphosphate is able to pass through this transparent layer and reach the detector. This means that there is essentially no background so a single dNTP incorporation can be detected.

On an entirely separate note, Vincent and Dickson have spoken on several occasions about a podcast about physics similar to TWIV. I only listen to four podcasts regularly including TWIV, TWIP and Futures in Biotech, but the fourth is one that I really think that you will enjoy. It is called Astronomy Cast (http://www.astronomycast.com/) and features two people, one an educated amateur (Frazier Cain) and the other an astronomy researcher (Dr Pamela Gay) discussing topics relating to astronomy, astrophysics, planetary geology, scientific history and cosmology, and even had a recent episode on exobiology in response to the arsenic incorporating bacteria story. As I write this, they are up to episode 210, each dealing with a particular topic, similar to your virology 101 episodes. The hosts also have their own blogs, as you do, and post many fascinating stories from the astronomy field (http://www.universetoday.com/ and http://www.starstryder.com/). I hope that you enjoy it.

Keep up the good work,

Jacob

Vince writes:

Hello

Although phage do not alter our health directly, they do provide novel genetic functions to their unicellular hosts, giving them access to new environments including the confines of our own bodies. My question is, can phage that are produced within our bodies transform otherwise harmless bacteria into pathogens? Or conversely, can phage produced by our endogenous microbiota infect other related invaders?

Thanks

Vince

Patricia writes:

Hello TWIV hosts!

I am a PhD student in Virology (Hepatitis C virus) at the University of Saskatchewan (Sus-KAT-choo-W'N, nobody says it right the first time), and I have been saving up comments for over a year now. Unfortunately, I have always neglected to send them in, because I am so frequently behind in my listening that I figure someone else will have said it before me! Plus, it's rather difficult to take notes or write emails when you're in the biosafety hood, which is where I listen to most of your 'casts - thus, most of my comments are kept in my head, a notoriously disorganzed place where it is easy to lose things.

That being said, I was actually reading Letters on the TWIV site, and realized that I can help respond to one of them (assuming you haven't already) while actually at my computer. Annamaria (in TWIV 114) asks about a site for people to post examples of things they have tried that have absolutely not worked. I have two links for you:

1) The Journal of Negative Results in BioMedicine: http://www.jnrbm.com/info/about/

This one is, of course, not for "I did a Western blot with this antibody and there was a lot of background," but moreso for "No matter what I tried, I could not demonstrate any interaction between this cellular protein and this viral protein." Still very useful for eliminating roads of investigation because others have tried them already.

2) Scientist Solutions: http://www.scientistsolutions.com/

This site is more immediately useful, as most protocols that people post are then treated as a blog, where they write back and forth, and folks can ask for clarification. It's a great way to get hints and help from very experienced people to very inexperienced people, and I fnd that I keep going back to it to look for more protocols.

And I've one other "immediate" comment to make:

With regards to recent comments from the TWIV - 10 of 2010 episode, I just wanted to point out a hazard of using microRNAs when we don't yet know "everything" - or at least, "enough" - about them. While the idea of using microRNAs to down-regulate or inhibit replication of an adenovirus vector in tissues outside the CNS is in principle quite clever, it could so very easily backfire. Hepatitis C Virus relies heavily on the liver-specific and liver-abundant miR-122 to enhance or permit its replication (which term to use is a matter of debate). What if a microRNA enhances the vector in a tissue rather than inhibiting it? We still don't know how microRNAs define whether to inhibit or enhance translation of mRNAs (they do both, although the enhancement findings are less common) - the suspicion is that it depends on where the microRNA-complementary site is on the mRNA, but that hasn't been fully defined yet.

(See: Ørom, U.A., F.C. Nielsen, and A.H. Lund. (2008). MicroRNA-10a Binds the 5'UTR of Ribosomal Protein mRNAs and Enhances Their Translation. Molecular Cell 30(4): 460-471.)

In the case of Hepatitis C virus, there are multiple miR-122 binding sites throughout the genome - two for sure at the 5' end, one whose binding has not been proven at the 3' end, and several proposed sites within the genome which have been presented at meetings but not yet published. Clearly, in this case, the enhancement (not of translation, but of replication) supercedes any inhibitory effect the microRNA might have.

Taking a different approach (I don't recall if this ever came up in TWIV), researchers have published a paper using an antagomiR (LNA that is complementary to miR-122 and should therefore mop it up) to inhibit this miR-122-mediated enhancement of HCV. The work was done in chimpanzees and they do show reduced viral titers while the LNA is still in the chimp's system.

Lanford, R.E., E.S. Hildebrandt-Eriksen, A. Petri, R. Persson, M. Lindow, M.E. Munk, S. Kauppinen, and H. Ørum. (2010). Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection. Science 327(5962): 198-201.

Thanks so much to all of you - VIncent, Alan, Rich, Dick - for your commitment to this podcast. You have made me smile and laugh to myself while in the hood (which makes me look like a crazy person, but oh well!), or shake my head and frown until someone catches a mistake, or re-explains something for me. You've made me - like many others - feel like we have a better grasp on the world of virology, outside of our own little niches. Above that, I get to share super-cool stories with my friends; sadly, they are less amused by some of the things that I find fascinating, but I keep trying! I hope you never, ever stop sharing with us.

Best regards,

Patricia

Kirsten writes:

I was wondering if a connection is being considered between the information presented by the Canadian group (TWIV 77) that correlates enhanced disease following flu vaccination in a percentage of cases and the data presented by Monsalvo et. al. (TWIV 112) that attributes enhanced disease to the presence of non-neutralizing antibodies and immune complexes. Could the non-neutralizing antibodies be present due to previous influenza vaccination?

Consider the RSV vaccine that was found to contribute to the presence of a low avidity, pathogenic antibody (TWIV 13), could there be a similar situation occurring?

Thanks,

Kirsten

Peter writes:

phage usage as an antibacterial cleaning solution

http://en.wikipedia.org/wiki/Intralytix

peter

Sydney

 

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