In the (herpes) virus model, a
stress-trigger activates a gene called
JNK, and JNK activates the dormant herpes virus causing it to replicate and spread.
According to this
paper (and
press release),
the herpes viruses are kept dormant by methyl groups attached to the virus DNA. Methyl groups act as the off-switch for the virus. When a gene called
JNK is activated, the methyl groups that were attached to the herpes DNA are eventually removed (demethylation). This DNA demethylation results in the virus replicating and spreading.
In this herpes model of POIS, as the virus spreads, the immune system attacks the herpes virus and herpes infected cells. The attack by the immune system on the virus causes inflammation and allergy, and you become sick. Therefore, in this virus model, POIS is an attack by a strong/healthy immune system on an invading/spreading pathogen (virus).
The immune system is doing exactly what it is supposed to do, which is kill the herpes virus and any infected cells.
An HHV-3 infected person with a
weak immune system would not get POIS. They would get shingles. Shingles occur when the immune system is weak and cannot fight the virus. And shingles can be triggered by stress.
The virus itself is not the main thing that makes you
feel sick, even though it is doing some damage to your body. What makes you feel sick (POIS) is the immune system releasing different molecules (histamine, cytokines, reactive oxygen species, antigens, etc...) to kill the virus.
Hi
Quantum,
Since JNK activation leads to the demethylation of herpes DNA, The spread of the virus can be stopped by methyl donors as long as you have a properly functioning
homocysteine cycle. Stopping the virus after it has already spread does not stop the immune system from attacking the newly deactivated virus. So genetic problems with methylation could be a confounding factor in POIS. Also there are different strands of HHV-3 and they have differing capacities to infect and spread. The chickenpox vaccine is a live virus strand of HHV-3, but it is the weakest know strand. So another possibility could be that those who are infected with stronger strands of the virus may experience more symptoms. Even if under-methylation or differences in HHV-3 strands are not unique factors for POIS, there could be other factors that are unique. Also, I thought you might be interested in this article "
COX-2 and PGE2 signaling is essential for the regulation of IDO expression by curcumin in murine bone marrow-derived dendritic cells"
Methyl groups attached to the viral DNA turn off the viral replication. However, when the methyl groups are removed (demethylation), the virus can activate/replicate. So methyl donors (choline and betaine) and B vitamins (B12, B9, etc...) play an important role in causing the herpes virus to go dormant.
Hi
Nas, My best guess now is that the stress-trigger for POIS (in the herpes virus model) is a combination of high prostaglandin E
2 (PGE
2) and low cyclic AMP. PGE
2 is found in high concentrations in semen and can cross the blood-brain barrier. I assume the dust from your dust allergy does not cross the blood-brain barrier. So I wouldn't expect dust to cause and herpes dependent POIS. Thank you for sharing that your POIS is induced by smoking. That helps narrow down the list of stress triggers.
Nicotine increases COX-2 and PGE2.
Desensitization treatments may work by exposing the body to chronically elevated levels of PGE
2 leading to gradual PGE
2 resistance (
Ref 1,
Ref 1,
Ref 3). This is analogous to how high insulin levels lead to insulin resistance (diabetes).
cyclic AMP is involved with erections.
JNK has many stress-triggers:
