Unintelligent Design - How Creationism's Intelligent [Sic] Designer Stupidly Competes With Itself In An Arms Race.

These microscope images show how interferon in the nucleus raises levels of the protective protein IFI16 (stained green) from low background levels (left) to the higher levels needed to resist herpes infection (right).

Image: HMS MicRoN core imaging facility/
Nicolas Romero Rata

Oral Herpes simplex

How the Immune System Fights to Keep Herpes at Bay | Harvard Medical School

Throughout the Cold War, starting soon after World War II and continuing through most of the second half of the 20th Century, the world's great powers, led by America on one side and Russia on the other, competed in a wasteful arms race where one side tried to outdo the other by building more powerful bombs and better delivery systems while also building better defences capable of preventing successful attack by the other. Money and resources that went into this ultimately pointless arms race could have been used for better, more peaceful projects like better world health care, better education or ending poverty and famine, yet neither side could afford to do the sensible thing because neither side trusted the other to abandon the race and compete with peace instead.

Although we can understand the pressures and insecurities that caused these wasteful arms races, we can also see the ultimate futility of it all and how the costs escalate with every turn of the spiral.

But how much more stupid would it have been if both 'sides' had the same people running them - if both America and Russia had the same political and military leaders? In other words, if the arms race was being run by one side alone, for no better reason than that the leaders had amnesia and didn't know why they built a bigger bomb or a better defence system yesterday and woke up today faced with a threat they had designed yesterday and needed to spend today designing ways to cope with these new threats?

One might be tempted to call into question the sanity of these leaders and wonder about their fitness to lead. What on Earth had allowed them to behave so stupidly? And for what reason? It certainly would have had nothing to do with the health and welfare or safety of the populations of Russia or America, or indeed the rest of the world, so could not be excused as some sort of well-intentioned altruism. An OCD or sheer malevolence, maybe, but not benevolence.

And yet creationists worship what they believe is a supernatural entity who behaves exactly like the amnesiac maniac I've just described. The natural world it reputedly designed, according to creationists, is full of example of these pointless and wasteful arms races for no ultimate long-term benefit to either 'side'.

I give many examples of these in my popular books The Unintelligent Designer: Refuting The Intelligent Design Hoax and the companion to it, The Malevolent Designer: Why Nature's God Is Not Good, and another example of it was published recently in Proceeding of the National Academy of Science (PNAS): This example concerns the state of play in the arms race between the human immune system that creationists will assure you was specially designed to protect us from the Herpes simplex viruses it specially designed to make us sick and increase the suffering in the world.

Creationism has a traditionally schizophrenic belief about the origin of viruses like Herpes simplex. On the one hand they will argue that the DNA in their genome is so complex that it should be regarded as proof of their supreme designer god because nothing else is capable of designing DNA; on the other hand they will argue that pathogenic parasites like viruses were not designed by their designer god but by something called 'Sin' because a mythical human founder couple, Adam & Eve, who were made by magic without parents, ate an apple. (I'm not joking!)

They cite some half-baked notion of 'genetic entropy', a term filched from thermodynamics and attached to 'genetic' to make it look nice and sciencey, and the biologically nonsensical notion of resulting 'devolution', invented by Michael J Behe of the Deception Institute to make it look like the myth of The Fall and real biology are compatible.

But, when pressed, creationists will argue that Adam & Eve were created with an immune system to protect them from the viruses and other pathogens that didn't exist when they were magicked into existence, so their designer god presumably knew what viruses were going to be like and how they worked!

Anyway, the immune system it allegedly designed didn't work very well since viruses and other pathogens still manage to make us sick and suffer and frequently prove fatal. For instance, the Herpes simplex virus isn't killed by the immune system and eliminated from the body, only rendered temporarily inactive, to reassert itself again later, as anyone who suffers from cold sores will testify.

Tell me about Herpes simplex, its origins and relationship to other viruses. Herpes simplex virus (HSV) is a family of DNA viruses that infect humans and other animals. There are two main types of herpes simplex viruses: HSV-1 and HSV-2.

1. Origins:
   • HSV-1: This type is typically associated with oral herpes, causing cold sores or fever blisters around the mouth and on the face. However, it can also cause genital herpes through oral-genital contact.
   • HSV-2: This type is primarily responsible for genital herpes, a sexually transmitted infection (STI).
The herpes simplex viruses have been infecting humans for a very long time, and their evolutionary history is complex. They are believed to have coevolved with humans, with evidence suggesting that HSV-1 has been present in the human population for thousands of years.
2. Relationship to Other Viruses:
   • Varicella-Zoster Virus (VZV): HSV is a member of the Herpesviridae family, and it is closely related to the varicella-zoster virus, which causes chickenpox and shingles. Both HSV and VZV are part of the alpha-herpesvirus subfamily.
   • Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV): These viruses also belong to the Herpesviridae family but are in different subfamilies. EBV is a member of the gamma-herpesvirus subfamily, while CMV is a beta-herpesvirus. Each herpesvirus subfamily has distinct characteristics and replication strategies.
   • Human Herpesviruses (HHVs): In addition to HSV, VZV, EBV, and CMV, there are other human herpesviruses, totaling eight known types. These include herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7), and Kaposi's sarcoma-associated herpesvirus (HHV-8).
   • Herpesvirus Structure and Replication: Herpesviruses share common structural features, including a large double-stranded DNA genome enclosed in an icosahedral capsid, surrounded by an envelope. They replicate in the nucleus of host cells, and their life cycle involves both lytic and latent phases.

It's important to note that while these viruses are related, they have distinct characteristics and can cause different diseases. The ability of herpes simplex viruses to establish latency and reactivate periodically contributes to their persistence in the human population and the recurrence of symptoms in infected individuals.

The discovery of how the human immune system tries to control and limit the spread of Herpes simplex was made by two researchers, Catherine N. Sodroski and Professor David M. Knipe, from Harvard Medical School. Their work is explained in a Harvard Medical School news release:

At a glance:

• In a study of lab-engineered cells, Harvard Med researchers identify how the immune system neutralizes the herpesvirus.
• The research maps, for the first time, the maneuvers used by virus and host in the cell nucleus, a poorly understood terrain of host-pathogen interaction.
• The findings could inform the design of new treatments for herpes and other viruses that replicate in the same way.

Herpes simplex virus (HSV) is extremely common, affecting nearly two-thirds of the world’s population, according to the World Health Organization.

Once inside the body, HSV establishes a latent infection that periodically awakens, causing painful blisters on the skin, typically around the nose and mouth. While a mere nuisance for most people, HSV can also lead to dangerous eye infections and brain inflammation in some people and cause life-threatening infections in newborns.

Researchers have long known that the virus and the host immune system are in a perpetual competition, but why does this battle reach a stasis in most people while causing serious infections in others?

Immune signaling proteins issue a call to arms

The research reveals a key role for a group of signaling proteins called interferons, which recruit other protective molecules and block the virus from establishing infection.

Once inside the host, HSV multiplies by making copies of itself inside the nuclei of cells, using the host’s genetic machinery. For that to happen, the virus must outcompete the host’s immune system. But many of the tactics the virus and the immune system use in this contest have remained a mystery, making it challenging to design medicines to help patients defeat the virus.

Interferons — named for their ability to interfere with pathogens’ attempts to infect cells — are signaling molecules released when the immune system detects the presence of microbes, such as viruses. The distress signals sent by interferons activate genes in that cell and other cells that produce proteins, which in turn block viruses from establishing infection in the first place.

Several different mechanisms that interferons use to thwart viruses within the cytoplasm, the gelatinous liquid that fills cells, are well known. But how interferons work against DNA viruses — those launching their attack within the cell nucleus — has remained elusive.

We know a lot about how interferon and immune stimulants work against viruses in the cytoplasmic body of the cell, but up until now, we knew very little about how the immune system blocks viral infection in the cell’s nucleus. Our findings define the mechanisms of action of any treatment that induces interferons and how they can prevent and treat infections from HSV, as well as other herpesviruses and nuclear DNA viruses.

Solving the puzzles that underlie the basic biology of how these viruses interact with the host cell nucleus and immune system is endlessly fascinating, and finding new ways to apply that knowledge to fighting diseases is endlessly rewarding. The most exciting part is that we’re just scratching the surface of the deep knowledge we can tap into for this fight.

Professor David M. Knipe, corresponding author,
The Higgins Professor of Microbiology and Molecular Genetics
Blavatnik Institute
Harvard Medical School, Boston, MA, USA.

Knipe said the insights from this work could also help researchers understand — and perhaps eventually develop treatments for — other nuclear DNA viruses, including well-known troublemakers like the Epstein-Barr virus, which causes mononucleosis; human papillomavirus; hepatitis B; and smallpox.

These results define the mechanisms of action of interferon treatments for herpesvirus diseases and other treatments such as toll-like receptor ligands that have been tested for herpes, the researchers said. Other new activators of interferons such as cGAS agonists could also be used to induce herpes resistance through the newly defined mechanisms, the researchers added.

The researchers caution that any new potential therapies for HSV and other DNA viruses are purely conceptual at this point. Any such approaches should be first tested in small animals such as mice, then in larger animals and, finally, in humans.

Mapping the steps of a viral arms race

In the new study, Knipe and co-author Catherine Sodroski, an HMS PhD graduate now at the National Institutes of Health, discovered that a host protein called IFI16 is recruited by interferon to help block the virus from reproducing in several ways.

One of the strategies used by IFI16 to fend off HSV involves building and maintaining a shell of molecules around the viral DNA genome. This molecular “bubble wrap” prevents the virus from unfurling. With the virus wrapped up, it can’t activate its DNA to express its genes and make copies of itself.

To counter these protective maneuvers, however, the virus produces molecules called VP16 and ICP0 that can remove the wrapping, deactivate the host cell’s protective molecules, and enable the virus to reproduce.

Another mechanism used by IFI16 to fight HSV infection is to neutralize VP16 and ICP016. Under normal circumstances, when the cell is not preparing to repel a viral invader, there is some IFI16 present within the nucleus. But this background level of IFI16 isn’t enough to fight off the viral helper proteins and keep the virus wrapped and restrained.

Without interferon’s call to the cell to send in more IFI16, the virus wins the arms race and infects the cell. However, the experiments showed, when interferon signals recruit higher levels of IFI16, the immune system wins.

This current study echoes similar findings that found elevated levels of IFI16 in clinical samples of tissues where the immune system appeared to be successfully controlling symptoms of the closely related HSV-2 virus, providing crucial insights about the molecular machinery at work in staving off outbreaks of symptoms.

Using insights from the lab to improve human health

Knipe says he became interested in the biology of herpesviruses as an undergraduate while recovering from a bout of mononucleosis. He turned that curiosity into a career.

The Knipe lab studies what happens at the level of molecules and cells when HSV causes symptomatic and dormant infections. He is particularly interested in how the host immune system responds to HSV. Knipe has applied the insights gained by studying HSV to explore the possibilities of using genetic material from HSV to deliver vaccines for HIV, SARS, West Nile, and anthrax.

Significance

Upon viral infection, cells produce and secrete proteins called interferons (IFNs) that bind to receptors on infected or neighboring cells to induce the expression of genes whose products act to interfere with viral replication. The mechanisms of action of certain of the IFN-induced proteins functioning in the cytoplasm have been defined, but little is known about the mechanisms of restriction of IFN-inducible proteins that act within the nucleus. In this study, we showed that a cellular nuclear protein, when induced by IFN, can reduce wild-type herpes simplex virus infection through effects on viral chromatin. This study defines the impact of this nuclear IFN-stimulated gene and provides opportunities for future antiviral strategies relating to epigenetic silencing within the nucleus.

Abstract

Interferons (IFN) are expressed in and secreted from cells in response to virus infection, and they induce the expression of a variety of genes called interferon-stimulated genes (ISGs) in infected and surrounding cells to block viral infection and limit spread. The mechanisms of action of a number of cytoplasmic ISGs have been well defined, but little is known about the mechanism of action of nuclear ISGs. Constitutive levels of nuclear interferon-inducible protein 16 (IFI16) serve to induce innate signaling and epigenetic silencing of herpes simplex virus (HSV), but only when the HSV infected cell protein 0 (ICP0) E3 ligase, which promotes IFI16 degradation, is inactivated. In this study, we found that following IFN induction, the pool of IFI16 within the infected cell remains high and can restrict wild-type viral gene expression and replication due to both the induced levels of IFI16 and the IFI16-mediated repression of ICP0 levels. Restriction of viral gene expression is achieved by IFI16 promoting the maintenance of heterochromatin on the viral genome, which silences it epigenetically. These results indicate that a nuclear ISG can restrict gene expression and replication of a nuclear DNA virus by maintaining or preventing the removal of repressive heterochromatin associated with the viral genome.

Sodroski, Catherine N.; Knipe, David M.
Nuclear interferon-stimulated gene product maintains heterochromatin on the herpes simplex viral genome to limit lytic infection Proceedings of the National Academy of Sciences (PNAS) 120 45 e2310996120. DOI: 10.1073/pnas.2310996120

Copyright: © 2023 The authors.
Published by PNAS.
Reprinted under a Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND 4.0).

Yet another example from the natural world for creationists to either ignore or lie about because it shows how, when you look beneath the superficial resemblance of design, there is no sentience in volved in the process that results in evolutionary arms races.

There is no 'good' or bad'; no 'right' and 'wrong' in the natural world, there is not even pitiless indifference because that implies sentience. There is only automatic, mindless response to change and opportunity. The notion of intelligent design is the result of scientifically, intellectually, morally and theologically bankrupt frauds trying to accommodate the scientific evidence that the childish superstitions they are using to fleece their gullible victims are wrong at every level and have no scientific credibility.

---

Thank you for sharing!

Tweet Link