Idea

Herpes as an immunity biomarker?

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jnikola Sep 07, 2020

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We are living in a busy world where we often experience the levels of stress that can have a devastating effect on our health. Do people go to doctors often enough or we need to develop home-based health tests? Do we already have visible biomarkers, reflecting the inner state of the organism, that can prevent further damage and prolong our healthspan? - Let´s discuss if herpes could work!

Herpes simplex virus (HSV) is the name of a set of viruses that infect around 67 % of the human population. The most common one is HSV-1, which usually causes watery cold blisters on the skin and mucous membranes in the area around and inside the mouth. In fewer cases of the reduced immune response, it can cause more significant symptoms. Once in the organism, the virus remains forever in neuron bodies, avoiding the immune system.

With the immune system being the number one protector of our body against viruses (throughout a system that keeps “records” of prior illnesses), it has a vital role in protecting against/controlling the HSV-1 infection. Many years ago scientists linked reoccurrence of cold sores caused by HSV-1 with a weakened immune system.

People often push themselves to work harder, longer, and without stopping to reach their (or their boss´s) goals. It is not uncommon that people push themselves too far and get seriously sick. 

Could we consider the (re)occurrence of the herpes blisters as a personal stress threshold that we can use to adjust our rhythm and habits in order to live healthier and reach the ultimate goal - live longer?

Would it allow us to recognize the moment when we need to boost our own defense with vitamins and a good rest, before the serious disease developed, or is it already too late then? 

If 67 % of the population is already infected with HSV-1, could it be advantageous instead of stigmatizing? Could we just infect everybody with HSV-1 and teach people what does it mean, or is it too dangerous?

We already inoculate weakened viruses to develop immunity (vaccination). If we somehow genetically engineer the virus so that it cannot cause serious symptoms and affect human healthspan, could we use it in standard vaccination?

Is there any alternative?
What are Your thoughts on this?

[1]https://www.who.int/en/news-room/fact-sheets/detail/herpes-simplex-virus

[2]https://www.coldsorescured.com/immune-system-and-cold-sores/; https://www.herpes-coldsores.com/immune-system.htm

immunology virus genetic engineering virology

Creative contributions

Biological risk and business interference

Martina Pesce Oct 27, 2020

The Herpes simplex virus type 1 and 2 (HSV1 and HSV2) with their natural features may not be the most indicated for this aim. Apart from the well known cold sores, among the side effects of HSV, there are (and I'm quoting the WHO):
 HSV-1 infection can rarely lead to more severe complications such as encephalitis (brain infection) or keratitis (eye infection)
Immunocompromised people can have more severe symptoms and more frequent recurrences
It enhances the chances of neonatal herpes which can lead to lasting neurologic disability or death in the future newborn
Infection with HSV-2 increases the risk of acquiring and transmitting HIV infection.

I'd say that already going for the HSV 1 instead of the 2 could be a good start.
As Juran also pointed out, there is research to identify and isolate the responsible mechanism of viral reactivation, and I'd say this is more of a way to go compare to the bare virus.
I have a concern though. Let's say we find this modified HSV to have a non-invasive marker for stress, which are the contras?
It would be great to have a biological proof to be excused from work for excessive stress, but the virus efficiency will never be 100%, so what happens if companies are going to blindly rely on it? Will they oblige all the employees to get infected with this virus? Even if it will be a free choice to do so or not, you may not be able anymore to find a job. If for some reason an individual is not responding to the infection, considering the inaccessibility of psychological help, how long will his stress and consecutive mental health be ignored? 

I'm worried about states where business rules it all. I think strict laws should really come along with an invention like this. 


I still believe it would be great: invisible negative health factors, such as stress, are too easily neglected.

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jnikola3 years ago

Thank you for joining the discussion. The main idea was to stress out that HSV infection can, except cold sores and and rare severe complications, be an amazing marker of immunity drop. 

As you mentioned, "invisible negative health factors, such as stress, are too easily neglected", and often cause different health issues. Therefore, IF you are infected, you can use it as a biomarker to help your future you to reduce the consequences of stress by avoid these highly stressful situations and states. Just an idea.

But I agree that before we ever think of vaccinating people with modified-HSV, we need proof it works (validation of these stressors reactivating the virus), proof it responds just to excessive stress (whatevet that means for each individual) and we need a way to perfectly control the virus. 

Stress is good for business and people who cope better with it, usually perform better. That could be a limitation of HSV vaccination, because then you would have measure of how you respond to certain amount of stress and how stressful you consider the situation. With that in mind, employer could selectively choose people who respond better. Although it would be good for employees, this should be followed by strict regulation, I agree.

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Update on HSV vaccine research

jnikola Nov 11, 2020

The problem of current vaccines is that
either vaccine doesn’t present enough antigens,
or the modified virus is so "sick" that it doesn’t work well to generate an immune response.
The "R2" vaccine 
A novel potential vaccine was developed by replacing five codons from each of the three regions of the HSV-1 genome that could be, according to the prior computer analyses, important in neuroinvasion - the main problem of the HSV treatment and lifetime occurrence.

Therefore, the R2 vaccine is live-attenuated HSV-1 encoding pUL37 tegument protein mutated in region 2. The vaccination of the R2 vaccine in mice and guinea pigs managed to amplify the presentation of the entire cohort of HSV antigens, without complications and the establishment of nervous system-based latent infections. It was also confirmed that the R2 vaccine decreases the rate of acute HSV-2 infection in guinea pigs.

Application
potentially good vaccine for HSV-1 (before the infection)
helps the research on the eradication of the HSV from the nervous system of the host - the importance of region 2

[1]https://www.nature.com/articles/s41541-020-00254-8

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Epigenetic findings on Herpesviruses

jnikola Oct 27, 2020

Research showed that DNA methylation is highly distributed on Kaposi's Sarcoma-Associate Herpesvirus genome. To be more specific, ORF50/Rta promoter is essential for the shift from latency to lytic replication, but not important in the maintenance of latent infection. ORF50 and Rta promoters are modified by activated H3K4me3 and repressive H3K27me3 during latent infection. Additionally, Rta demethylation induces lytic infection in vivo. HDAC1, HDAC5, and HDAC7 repress the Rta promoter during its latency. More factors such as histone modifications, non-coding RNAs (miRNAs), and chromatin remodellers were also introduced to have a role in herpesvirus 'switch' from latency to lytic infection .

Further research on epigenetics of the viral infection and latency is needed. But, by understanding the roles of viral and host factors in this 'switch' (demethylation, inhibition, repression, activation, etc.), we would be able to "track" and find the baseline changes that trigger the virus reactivation. These findings could help determining the key processes usually called "the stress/drop of immunity".

[1]https://www.annualreviews.org/doi/pdf/10.1146/annurev-virology-020420-014025

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HSV1 in saliva as a marker of abrupted immunity

jnikola Dec 02, 2022

The researchers did a study on the relationship between Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and SARS-CoV-2 infection and found significant upregulation of Herpes Simplex Virus 1 (HSV1) IgG (and some other) within the same individuals when comparing antibody levels before and after SARS-CoV-2 infection. It was another evidence that infection can trigger the reactivation of latent "symbiotic" viruses by activating a strong immune response. It is interesting that SARS-CoV-2 infection generated a distinct antibody fingerprint of latent virus reactivation in saliva, but not in plasma. 
These findings support the usage of HSV1 from saliva for the approximation of the immunity state of the organism. Since the positive saliva test doesn't necessarily mean the presence of visual HSV1 ulcers, it presents a more sensitive method for fast immunity check.
How could this be applied?
I imagine it as a fast antigen swab test similar to COVID-19, which delivers results in several minutes and is positive if the titre of Herpes Simplex Virus 1 (HSV1) IgG is higher than threshold defined as a borderline between normal and abrupt immunity. 