3 replies to this topic

[xEva]

I'd like to discuss herpesviruses and autophagy -- specifically, how they may interfere (or be helped) with fasting.

I came across a number of papers which I'd like to discuss. So far, posting just one:

The Unfolded Protein Response and Autophagy: Herpesviruses Rule! 2008
Dong Yun Lee, Jisook Lee and Bill Sugden

 

The unfolded protein response (UPR) and autophagy are two cellular environmental responses that affect a cell's life or death. The UPR begins on the sensing of an excess of unfolded proteins in the endoplasmic reticulum (ER). Autophagy, originally discovered as a response to nutrient depletion, is involved in development, in the degradation of cellular components, and in the reaction to intracellular bacteria and viruses. Some herpesviruses now appear to modify one or both of these responses to their own advantages during productive and latent infections. We know that the UPR can be mechanistically linked to autophagy, prompting the notion that herpesviruses may modify both responses by regulating one or that they may even uncouple them.

 

[albedo]

Fascinating xEva!

 

In gene therapy, using viruses as vectors for gene transfer, you possibly transient-inhibit UPR and possibly autophagy. E.g. it is known metformin can be used to lower UPR hence I wonder that IF might work by similar paths. Does it make any sense? What is the main path IF works? I cannot believe it might be helping HSV outbreaks.

 

 “…One of the ways to inhibit UPR is through small molecule inhibitors, which can repress the cellular proteasomal machinery. For example, the use of pharmacological agents that inhibit proteasomes like metformin, MG-132, and ricin has been previously shown to reduce cellular UPR (Lee et al., 2003; Parikh et al., 2008; Amanso et al., 2011; Theriault et al., 2011)…”

 

“…Most viruses reprogram the cellular translational machinery to facilitate the generation of their proteins, but this process can also trigger the UPR pathways, which consequently may lead to cell death. For successful gene therapy, the survival of the transduced cells is very important to achieve sustained gene expression. In this scenario, transient inhibition of UPR prior to gene transfer, by strategies discussed above, provides an attractive alternative to improving the safety and efficiency of viral gene therapy…”

 

Cellular unfolded protein response against viruses used in gene therapy

http://www.ncbi.nlm....les/PMC4033601/

Edited by albedo, 05 March 2016 - 09:14 PM.

[xEva]

That's interesting what you posted. But I'm not ready it yet to start down- or upregulating anything. I have some questions first.
 

In gene therapy, using viruses as vectors for gene transfer, you possibly transient-inhibit UPR and possibly autophagy. E.g. it is known metformin can be used to lower UPR hence I wonder that IF might work by similar paths. Does it make any sense? What is the main path IF works? I cannot believe it might be helping HSV outbreaks.

Indeed, how deep a fast should be to trigger a latent or an idling virus?

See, in my experience, I don't recall having HSV-1 outbreaks triggered by a fast. It's hard to say about CMV and EBV, because they don't manifest in blisters on your mouth, where you can't miss them -- though I heard that either CMV or EBV (or both?) can trigger a rash on the body. I know for sure that HSV-1 can be triggered by a sun overdose, because I have experienced it, more than once. It can also be triggered by cold -- there is a reason it's called a 'cold sore'. But I don't recall it flaring up from just fasting.

But maybe someone else had different experience?

Regarding IF, the question, for me at least, is when does this 'triggering' level of autophagy start. I had extensive experience with another virus, HCV (all in the past, thank God!), and know when it starts going crazy. I noticed this long before I read the papers that HCV exploits autophagy for its own proliferation: people with active HCV can't fast longer than 3 days. At most, they last till the end of the 4th day, but in reality they should not even dip their toes in ketosis, which means that they should fast maximum 36-48h. Experience shows that short fasts, 24-36h weekly, are very beneficial for just about anything, even for HCV. Much longer, "real" fasts may also prove beneficial for HCV in the end, but the viral load may go through the roof (it's 'cause viral load is just one variable in this benefit-cost ratio).

So, back to herpesviruses. Based on experience with a different virus, I would guess --in lieu of hard data of any kind-- that the "real" autophagy, the kind that can trigger something unusual in a human, starts with the onset of ketosis, which follows immediately after the depletion of liver glycogen, which in most people starts 36-48h after the last meal. What do you guys think?

I expect some "scientifically minded" participants objecting to my approach, but I'd like to point out that neither in vitro nor mice studies will tell you what you need to know. And it's hard to say from the papers (I'll post more later). All intracellular pathogens trigger autophagy --that's a normal response to them. Is it misleading for some authors to make it sound as if there more to it, at least with some viruses? I'm not too sure about any of this at the moment.

Edited by xEva, 06 March 2016 - 06:58 AM.

[aconita]

Indeed, how deep a fast should be to trigger a latent or an idling virus?

 

Since fasting is a stress as any other stress it down regulates the immune system to the point where viruses are not kept under control and will outbreak, how deep a fast should be to cause that is probably dependent by many factors such as immune system strength, other concomitant stressors, individual stress response to fasting (somebody used to ketosis would perceive fasting as less stressful than someone else whom lives on high carbs diet).