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Monday, 17 July 2017 08:22

TWiV 450 Letters

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Published in Letters

Hitoshi writes:

The correct pronunciation for “Tentomushi” is like ten-toe mushi, not ten-two (10-2) mushi.

Paul writes:

Twivoli:

An Excessive heat warning covers SE PA for tomorrow but presently 32C with 50% and 27m/h winds.

Thanks for episode 449.

One question and one comment.

Question:

The article discussed the method a mammalian virus used to suppress RNAi suppression.  It implied that RNAi could be common in mammals but routinely suppressed by mammalian viruses.  In any event it definitely identified a fairly straightforward RNAi suppression mechanism available to RNA viruses. So, why wouldn’t such a suppression mechanism be common in plant and invertebrate viruses that face RNAi as their primary barrier to success.

Comment:

Ockham’s Razor originally referenced  primarily that “Entities [i.e. hypothetical entities] must not be multiplied beyond necessity”; this is different from a general bias in favor of simpler hypotheses. For example, the Razor would prefer a more complex hypothesis that hypothesized one enzyme to a simpler hypothesis that required two.

Great content.

Chris Sullivan writes:

Dear TWiV Hosts,

I am glad that you are dedicating back-to-back episodes to cover the exciting topic of RNA silencing and antiviral defense in vertebrates, something my lab thinks about. As you mentioned us in the previous episode TWIV#449 for possible comment, I thought I would briefly respond. This paper by Qiu et al., similar to recent work from Cullen and Ding labs, clearly demonstrates siRNAs matching viral sequence can arise in mammalian cells at least at some level in the right context. It also provides further genetic evidence consistent with an antiviral activity of RNAi. I think a picture is emerging in the field as a whole that there are at least some hallmarks of antiviral RNAi in mammals. The debate now moves from “do these hallmarks ever exist?” to “how meaningful are they?”.

Although the issue of whether RNAi is a relevant mammalian antiviral response still remains unresolved, I think all parties can agree that some hallmarks of antiviral RNAi exist but are more context dependent and limited in mammals. Whatever your favorite take on the larger issue of antiviral mammalian RNAi, I think most would also agree that RNAi is clearly different between mammals and invertebrates. Whether due to differences in the effectiveness of mammalian versus invertebrate VSRs, or more likely in my opinion, due to the differences between mammalian and invertebrate host biology, viral derived siRNAs are of lower abundance and likely less importance in mammalian cells infected with WT virus. Further, our own published and unpublished work, combined with work from numerous labs (including the Pfeffer, Cullen, and Sousa labs) shows that there are clashes between the effectors of the protein-based mammalian antiviral response (e.g., RNase L, PKR, IFN) and multiple components of the RNAi machinery. Thus, it remains unclear to me how much antiviral RNAi matters in mammals where the protein based response appears to have superseded and even counters components of RNAi.

It has been fun to watch the science unfold around this issue over the years. Yes, the dialog has been heated at times, but as long as this is kept to debate about the data and its interpretation, this is what makes science work. I commend all parties for the strife they have endured to stand up for their perspectives when, as too often happens, it would be easier and less risky to just ignore those papers you don’t agree with. Antiviral mammalian RNAi is an important issue, and I am glad the discussion continues. This is good for science and gets us closer to true understanding.

As always, thanks to all of you for what you do. Listening to you is one of the enjoyable parts of my job.

Chris

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