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Viruses may be 'watching' you – some microbes lie in wait until their hosts give them the signal to start multiplying

16 Comments
By Ivan Erill

After more than two years of the COVID-19 pandemic, you might picture a virus as a nasty spiked ball – a mindless killer that gets into a cell and hijacks its machinery to create a gazillion copies of itself before bursting out. For many viruses, including the coronavirus that causes COVID-19, the “mindless killer” epithet is essentially true.

But there’s more to virus biology than meets the eye.

Take HIV, the virus that causes AIDS. HIV is a retrovirus that does not go directly on a killing spree when it enters a cell. Instead, it integrates itself into your chromosomes and chills, waiting for the right moment to command the cell to make copies of it and burst out to infect other immune cells and eventually cause AIDS.

Exactly what moment HIV is waiting for is still an area of active study. But research on other viruses has long hinted that these pathogens can be quite “thoughtful” about killing. Of course, viruses cannot think the way you and I do. But, as it turns out, evolution has endowed them with some pretty elaborate decision-making mechanisms. Some viruses, for instance, will choose to leave the cell they have been residing in if they detect DNA damage. Not even viruses, it appears, like to stay in a sinking ship.

My laboratory has been studying the molecular biology of bacteriophages, or phages for short, the viruses that infect bacteria, for over two decades. Recently, my colleagues and I have shown that phages can listen for key cellular signals to help them in their decision-making. Even worse, they can use the cell’s own “ears” to do the listening for them.

Escaping DNA damage

If the enemy of your enemy is your friend, phages are certainly your friends. Phages control bacterial populations in nature, and clinicians are increasingly using them to treat bacterial infections that do not respond to antibiotics.

The best studied phage, lambda, works a bit like HIV. Upon entering the bacterial cell, lambda decides whether to replicate and kill the cell outright, like most viruses do, or to integrate itself into the cell’s chromosome, as HIV does. If the latter, lambda harmlessly replicates with its host each time the bacteria divides.

But, like HIV, lambda is not just sitting idle. It uses a special protein called CI like a stethoscope to listen for signs of DNA damage within the bacterial cell. If the bacterium’s DNA gets compromised, that’s bad news for the lambda phage nested within it. Damaged DNA leads straight to evolution’s landfill because it’s useless for the phage that needs it to reproduce. So lambda turns on its replication genes, makes copies of itself and bursts out of the cell to look for more undamaged cells to infect.

Tapping the cell’s communication system

Some phages, instead of gathering intel with their own proteins, tap the infected cell’s very own DNA damage sensor: LexA.

Proteins like CI and LexA are transcription factors that turn genes on and off by binding to specific genetic patterns within the DNA instruction book that is the chromosome. Some phages like Coliphage 186 have figured out that they don’t need their own viral CI protein if they have a short DNA sequence in their chromosomes that bacterial LexA can bind to. Upon detecting DNA damage, LexA will activate the phage’s replicate-and-kill genes, essentially double-crossing the cell into committing suicide while allowing the phage to escape.

Scientists first reported CI’s role in phage decision-making in the 1980s and Coliphage 186’s counterintelligence trick in the late 1990s. Since then, there have been a few other reports of phages tapping bacterial communication systems. One example is phage phi29, which exploits its host’s transcription factor to detect when the bacterium is getting ready to generate a spore, or a kind of bacterial egg capable of surviving extreme environments. Phi29 instructs the cell to package its DNA into the spore, killing the budding bacteria once the spore germinates.

In our recently published research, my colleagues and I show that several groups of phages have independently evolved the ability to tap into yet another bacterial communication system: the CtrA protein. CtrA integrates multiple internal and external signals to set in motion different developmental processes in bacteria. Key among these is the production of bacterial appendages called flagella and pili. Turns out, these phages attach themselves to the pili and flagella of bacteria in order to infect them.

Our leading hypothesis is that phages use CtrA to guesstimate when there will be enough bacteria nearby sporting pili and flagella that they can readily infect. A pretty smart trick for a “mindless killer.”

These are not the only phages that make elaborate decisions – all without the benefit of even having a brain. Some phages that infect Bacillus bacteria produce a small molecule each time they infect a cell. The phages can sense this molecule and use it to count the number of phage infections taking place around them. Like alien invaders, this count helps decide when they should switch on their replicate-and-kill genes, killing only when hosts are relatively abundant. This way, the phages make sure that they never run out of hosts to infect and guarantee their own long-term survival.

Countering viral counterintelligence

You may be wondering why you should care about the counterintelligence ops run by bacterial viruses. While bacteria are very different from people, the viruses that infect them are not that different from the viruses that infect humans. Pretty much every single trick played by phages has later been shown to be used by human viruses. If a phage can tap bacterial communication lines, why wouldn’t a human virus tap yours?

So far, researchers don’t know what human viruses could be listening for if they hijack these lines, but plenty of options come to mind. I believe that, like phages, human viruses could potentially be able to count their numbers to strategize, detect cell growth and tissue formation and even monitor immune responses. For now, these possibilities are only speculation, but scientific investigation is underway.

Having viruses listening to your cells’ private conversations is not the rosiest of pictures, but it’s not without a silver lining. As intelligence agencies all around the world know well, counterintelligence works only when it’s covert. Once detected, the system can very easily be exploited to feed misinformation to your enemy. Similarly, I believe that future antiviral therapies may be able to combine conventional artillery, like antivirals that prevent viral replication, with information warfare trickery, such as making the virus believe the cell it is in belongs to a different tissue.

But, hush, don’t tell anybody. Viruses could be listening!

Ivan Erill is a professor in the Biology department at University of Maryland, Baltimore County.

The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.

© The Conversation

©2022 GPlusMedia Inc.

16 Comments
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This is a very interesting field of study and it can be important even for human therapies. For the development of human viral vectors that deliver gene therapy it is very important to get as much of those viruses as possible with the least amount of complications and money, so the therapies using them do not become so expensive nobody can use them.

Classically this meant cultivating the viruses in cells being growth with as much care as possible, so nothing affects the viral replication (made weak on purpose so the vectors are safe for humans). That have changed now that research have demonstrated viruses replicate more when the cells receive some damage as described in the article, so cultivating cells with a different pH, or less nutrients makes them receive a limited amount of damage and this increase the production of the vectors.

-4 ( +4 / -8 )

It's as if a whole swath of humanity has had their immune systems compromised in some way.

No, it is not. Efforts to control infectious disease of global important have decreased because of the pandemic, so obviously an increase of cases has been expected without any kind of forced theory to explain it.

The same happens with diseases that depend on congenital malformations, less than healthy life styles or pollution. Nobody wonders why this happens nor the experts are blaming some compromise of the immune system.

-4 ( +4 / -8 )

It’s as if a whole swath of humanity has had their immune systems compromised in some way

Ah, yes. This poster stirring the pot as always, joining up the dots on pictures invisible to anyone else, followed up by wild assertions on his pet topic with no links to any proof or to reality as most of us know it.

I’m getting to quite enjoy it, actually, it’s as reliable and comforting as the snow on the steppes in wintertime.

-3 ( +4 / -7 )

People should learn from this. Where does the fake science come from?

0 ( +1 / -1 )

It's as if a whole swath of humanity has had their immune systems compromised in some way.

Some doctors are baffled.

Others... not so much.

Don’t be shy, say what you are thinking.

Or is it one of the those top secret truths that only a select few know and is too dangerous to share?

0 ( +4 / -4 )

The idea that a virus "Lies in waiting" is not new.

Lots of research has been done on the "stealth" of the Herpes virus ( in all it's incarnations).

The ubiquitous Herpes virus is surely responsible directly or indirectly for many of modern humans various health afflictions.

1 ( +2 / -1 )

Phages control bacterial populations in nature, and clinicians are increasingly using them to treat bacterial infections that do not respond to antibiotics.

This is true. And bacteriophages exist wherever bacteria exist. They are estimated to be more than every other organism on Earth. It is important to know that phages do not infect humans,  They are targeted bacterial viruses that have multiple antibacterial effector functions that can reduce multidrug-resistant infections in people.

Efforts to control infectious disease of global important have decreased because of the pandemic, so obviously an increase of cases has been expected without any kind of forced theory to explain it.

This is true, as the WHO, for example, took their eye off the ball on the malaria crisis. Another error the WHO made was to reduce the focus on household insecticide spraying to interrupt malaria transmission.

Nobody wonders why this happens nor the experts are blaming some compromise of the immune system.

Obviously this is not a medical or scientific conclusion.

-5 ( +1 / -6 )

This is true, as the WHO, for example, took their eye off the ball on the malaria crisis. 

Which is understandable and desirable, because a bigger more urgent matter had to be dealt with immediately to prevent even worse consequences. That is not an error, it is a negative consequence of the pandemic even if you personally want to consider everything the WHO does as a mistake even if the experts working on the field do not support that personal judgment. Reducing the use of insecticide on houses to be replaced by more effective and less risky interventions (like Insecticide-impregnated bed nets) is not a mistake either.

Obviously this is not a medical or scientific conclusion.

Since you make no argument to demonstrate it so, this is again just something you don't want to accept but you can't disprove either, so you make a baseless appeal to your own authority to decide this, which of course has not validlty.

0 ( +2 / -2 )

Another error the WHO made was to reduce the focus on household insecticide spraying to interrupt malaria transmission

That is true. But you forget that they also messed up on masks at the beginning. And another error is they snuggled up to China at the beginning. Don't forget all that.

2 ( +3 / -1 )

And another error is they snuggled up to China at the beginning. 

More on that for your information, China was being praised by WHO for its success on beating the coronavirus. Very silly for the WHO, because...

Another error; China's insistence on adhering to a so-called Covid Zero policy is leaving it increasingly isolated as other countries that suffered far-worse outbreaks return to a semblance of per-pandemic life.

Why is that an error?

Because, other country's populations have built up a large degree of protection against serious illness - and reduced the initial fear of the unknown -through waves of infections and more-effective vaccines.

The pickle China is now is the their fault as the pandemic might be ending for some, it's only stating for China.

0 ( +1 / -1 )

....more-effective vaccines.

Huh?

0 ( +0 / -0 )

Viruses may be 'watching' you – some microbes lie in wait until their hosts give them the signal to start multiplying

This is common knowledge. The viruses on the small scale look for a healthy environment to invade.

This is true, as the WHO, for example, took their eye off the ball on the malaria crisis. 

Which is understandable and desirable, because a bigger more urgent matter had to be dealt with immediately to prevent even worse consequences. 

How is it desirable to have deaths attributed to malaria (600,000) considerably higher than deaths attributed to Covid-19 (less than 200,000)? This not not a scientifically accurate analysis. Global experts don't agree with that "assessment."

Reducing the use of insecticide on houses to be replaced by more effective and less risky interventions (like Insecticide-impregnated bed nets) is not a mistake either.

Let's see statistics that back up your claim.

Elvis is hereSep. 21  09:13 am JST

The pickle China is now is the their fault as the pandemic might be ending for some, it's only stating for China.

China is doing what they have been doing for almost three years. And without the millions of deaths that the West incurred.

-4 ( +0 / -4 )

China is doing what they have been doing for almost three years. And without the millions of deaths that the West incurred.

The accumulated death toll in "the west" compared to a false reported toll in China is hardly a valid comparison. Chinas immunity is a big problem. The Pandemic has only started in China. Zero policy is inhuman and is prolonging and exaggerating a serious health crisis. That is nothing to champion.

2 ( +2 / -0 )

How is it desirable to have deaths attributed to malaria (600,000) considerably higher than deaths attributed to Covid-19 (less than 200,000)? This not not a scientifically accurate analysis. Global experts don't agree with that "assessment."

Mainly because your information is false, deaths attributed to covid are over 6 million, and that is with emergency measures put forward that limited the number to a fraction of what would have happened if covid was not made a priority.

This not not a scientifically accurate analysis. Global experts don't agree with that "assessment."

Again making an appeal to global experts you can never bring? that is (the same as every time you do this) still an empty excuse you are trying to use to push your personal opinion as if it came from someone with actual authority.

Let's see statistics that back up your claim.

See, there is nothing wrong with recognizing you ignore completely a topic and that is why you make wrong judgments, this is elementary for people actually involved with malaria and is not even something new

https://www.cdc.gov/malaria/malaria_worldwide/reduction/itn.html

China is doing what they have been doing for almost three years. And without the millions of deaths that the West incurred.

But with more deaths than some countries that have never had to destroy the livehood of the people in the site of an oubreak, that never had to let people die because they interrupted access to health services and without completely erasing human rights and abuse their power to harrass people using the policy as an excuse. This means the measures are unnecessary to get even better results than China, and all according to the same sources you brought to mistakenly say the opposite.

0 ( +1 / -1 )

Mainly because your information is false, deaths attributed to covid are over 6 million, and that is with emergency measures put forward that limited the number to a fraction of what would have happened if covid was not made a priority.

Nope. As noted, Africa experienced more deaths by malaria than Covid 19:

Africa recorded over 600,000 malaria deaths in 2021, says WHO

https://newsdigest.ng/africa-recorded-malaria/#:~:text=NEWS%20DIGEST%20–%20The%20World%20Health%20Organization%20%28WHO%29,the%20estimated%20228%20million%20cases%20of%20the%20disease.

See, there is nothing wrong with recognizing you ignore completely a topic and that is why you make wrong judgments, this is elementary for people actually involved with malaria and is not even something new

https://www.cdc.gov/malaria/malaria_worldwide/reduction/itn.html

Nice! Your own source supports my statement about how the WHO mistakenly advised reducing insecticide use!!

Insecticide-treated bed nets (ITNs) are a form of personal protection that has been shown to reduce malaria illness, 

-2 ( +0 / -2 )

Nope. As noted, Africa experienced more deaths by malaria than Covid 19:

And again, that is not the total number of deaths that happened in the world, it is the WHO, no the AHO. And once again this is the number of deaths produced while life changing measures were put in place, which means that not making covid a priority as it was done would have resulted in much higher deaths.

Nice! Your own source supports my statement about how the WHO mistakenly advised reducing insecticide use!!

No, it did not, that mistake is completely yours, you said it was a mistake to reduce insecticide spraying in houses, but that is no mistake because the use of impregnated nets is a much efficient use which is why the WHO recommends FOR using it instead of spraying, which means you are still wrong on this because you did not understand that spraying is old, inefficient and riskier compared with the use of nets.

So you are still wrong on that, you just did not understand why.

Also, where are the experts that you said disagreed? you brought exactly zero of them, are you accepting they don't actually exist?

0 ( +0 / -0 )

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