Unintelligent Design - The Divine Loser - Or How Creationism's Divine Malevolence Was Just Too Clever

Structure of Venezuelan Equine Encephalitis Virus

Ma, B., Huang, C., Ma, J. et al. (2021)

Evolution Tamed Once-Deadly Western Equine Encephalitis. Should We Still Worry? | Harvard Medical School

Creationism's divine malevolence is nothing if not sneaky and underhand, so we always need to be wary of what it is up to. For instance, following its early success with the western equine encephalitis virus (WEEV) in the early part of the 10th century, the virus seems to have lost its virulence and stopped infecting humans and horse, spending all its time in the body of the birds that were its reserve hiding places when it was at its most dangerous in the early 20th century.

The virus was spread by the divine malevolence’s favourite insect vector - mosquitoes, especially the usual suspects, the Culex and Aedes genera. In 1941 it accounted for3000 human cases with a mortality rate of 3-7%, but such has been its decline that there were only 600 human cases between 1964 and 2009 in the USA.

But is its designer merely biding its time and waiting for another chance to launch another attack on us, or is this an example of the malevolent designer being just a bit too clever, and having a plan that wasn't worth the paper on which it was written? We had a warning against complacency last year with an outbreak in Argentina and Uruguay with 2.400 horse cases and 103 human cases with a 10% morality rate in humans.

Tell me all about Western Equine Encephalitis, please. Western Equine Encephalitis (WEE) is a viral disease affecting horses, humans, and birds, primarily in North America. Here's a comprehensive overview:

Causative Agent

WEE is caused by the Western Equine Encephalitis virus (WEEV), a member of the genus Alphavirus in the family Togaviridae.

Transmission

• Vectors: The primary vectors for WEEV are mosquitoes, especially those of the Culex and Aedes genera.
• Reservoir Hosts: Birds, particularly passerine birds, serve as the primary reservoir hosts for the virus.
• Horses and Humans: Both can become infected when bitten by an infected mosquito, but they are considered dead-end hosts, meaning they do not contribute to the further spread of the virus.

Epidemiology

• Geographic Distribution: WEE is found mainly in the western United States, western Canada, and parts of Central and South America.
• Seasonality: Outbreaks typically occur in the summer and early fall when mosquito activity is at its peak.

Clinical Signs and Symptoms

• In Horses: Symptoms can range from mild fever and lethargy to severe neurological signs such as ataxia (lack of coordination), circling, head pressing, blindness, seizures, and paralysis. The mortality rate in horses can be as high as 20-50%.
• In Humans: The majority of human infections are asymptomatic or result in mild flu-like symptoms. In severe cases, symptoms can include high fever, headache, stiff neck, vomiting, confusion, and seizures. Neurological involvement can lead to encephalitis (inflammation of the brain), which can be fatal or cause long-term neurological deficits. The mortality rate in humans is lower than in horses, typically around 3-7%.

Diagnosis

• Clinical Signs: Diagnosis in horses and humans is based on the observation of clinical symptoms, especially neurological signs.
• Laboratory Tests: Confirmation requires laboratory testing, such as:
  • Serology: Detection of antibodies against WEEV in blood or cerebrospinal fluid.
  • PCR: Detection of viral RNA using polymerase chain reaction.
  • Virus Isolation: Culturing the virus from blood or tissue samples.

Treatment
There is no specific antiviral treatment for WEE. Supportive care is the mainstay of treatment and may include:

• In Humans: Hospitalization, intravenous fluids, respiratory support, and measures to reduce intracranial pressure.
• In Horses: Anti-inflammatory drugs, intravenous fluids, and supportive care.

Prevention

• Mosquito Control: Reducing mosquito populations through habitat modification, insecticides, and use of mosquito repellents.
• Vaccination: Vaccines are available for horses and are highly effective in preventing WEE. There is no vaccine for humans.
• Personal Protection: Wearing long sleeves, using insect repellent, and avoiding outdoor activities during peak mosquito activity times.

Public Health Impact
WEE is a rare but potentially serious disease. Public health efforts focus on surveillance, mosquito control, and education to prevent outbreaks.

Historical Context

• WEE was first recognized in the early 20th century and has caused periodic outbreaks, especially in the mid-20th century in the United States and Canada.
• Modern mosquito control and vaccination programs for horses have significantly reduced the incidence of the disease.

Recent Developments
Research continues into better understanding the ecology of WEEV, improving diagnostic methods, and developing new strategies for prevention and control.

By understanding these aspects of Western Equine Encephalitis, measures can be taken to reduce the risk of infection and manage outbreaks effectively.

Although still capable of a comeback, the reason for the viruses. decline seems to have been a design error, if you believe these things are designed and don't evolve naturally. Faced with growing resistance in its bird reservoir species, the virus was redesigned to make it easier to infect birds, but in doing so, the redesigned virus was able to infect mammals only with difficulty.

An examination of the modern virus and comparing it with samples from the height of the epidemic shows that the virus has had some significant changes which make it better able to live and replicate in birds, but less able to attack horses and humans where it did most of its damage. The changes were to the virus spike protein in its surface that is uses to bind to receptors on the cell surface and prize an opening.

Unusually for a virus, which are usually host-specific, this spike protein could bind to receptors of horse, human and bird cells. Not only that but they could bind to two other proteins, known as PCDH10 and VLDLR, found on the surface of brain cells in humans and horses but not birds. The modified virus lost the ability to bind to these proteins.

The changes that made it better at infecting birds meant it could no longer bind so easily to the mammal cells.
This was discovered by a research team at Harvard Medical School, who have just published their findings, open access, in the journal Nature. It is explained in a press release from Harvard Medical School by Jake Miller:

Evolution Tamed Once-Deadly Western Equine Encephalitis. Should We Still Worry?

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The fate of a mutating virus offers important clues for pandemic preparedness

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At a glance:

• Over the last century, a once-deadly mosquito-borne virus has evolved so that it no longer sickens humans.
• New research shows that changes in the virus’s ability to target human cells paralleled the decline in illness and death.
• The findings offer important lessons in virology that may help guide better preparedness for future outbreaks of other viral diseases.

The story of the rise and fall of western equine encephalitis as a lethal disease offers essential lessons about how a pathogen can gain or lose its ability to jump from animals to humans.

That story is captured in newly published research from Harvard Medical School that identifies the mechanisms the western equine encephalitis virus used to infect humans and matches changes in that ability over time to a decline in illness and deaths caused by the pathogen.

The study results, published July 24 in Nature, offer important lessons for public health experts looking to prepare for future outbreaks, the researchers said.

The work took many unexpected turns, the researchers said. The findings challenge some of the basic assumptions that scientists have relied on in their attempts to understand how viruses interact with human cells and what causes outbreaks to ebb and flow, such as the notion that any given virus targets one host receptor to gain entry and infect cells.

This was a real scientific detective story. The virus kept surprising us and taught us some important lessons about how to study viruses.

Associate Professor Jonathan Abraham,
Associate professor of microbiology
Blavatnik Institute
Harvard Medical School
Boston, MA, USA.

The researchers identified the specific proteins expressed on host cells that different strains of the virus have used to infect a variety of animals, including horses, humans, and birds over the last century. Their findings tied differences in the virus’s ability to sicken humans and horses to changes in the viral genome that left the virus unable to target proteins found in humans and horses, while leaving intact the virus’s ability to infect birds and reptiles that serve as reservoirs for the virus.

The surprising diversity and variability in the virus’s ability to infect host cells highlights the importance of studying viruses broadly across time, space, and host species to track potential outbreaks and monitor for emerging and re-emerging viruses.

A virus changes

The protagonist in the story is the western equine encephalitis virus (WEEV), a member of a viral family known as alphaviruses.

One key to understanding how a virus interacts with a host is identifying the precise path it takes to enter cells and cause infection.

WEEV and others in the alphavirus family typically attach a spike protein to a compatible protein — the receptor — on the surface of a host cell. Once attached to the host receptor, the virus enters the cell. Once inside the cell, the virus hijacks the cells’ armamentarium to enable its own replication, spread, and survival.

The researchers made harmless replicas of various viral strains collected from different times and places and tested their ability to infect host cells in lab dishes. They also tested some of the strains in mice.

Several deadly strains of WEEV are known to cause severe brain inflammation in both horses and humans. Some years, thousands of horses were killed and hundreds of humans were sickened. Case fatality rates for people were as high as 15 percent in North America in the early and middle decades of the 20th century.



Abraham’s group found that some of these early strains could stick their spike proteins to several different types of receptors to enter animal cells. That was an unexpected finding because the prevailing dogma in virology thus far has been that viruses typically attack by targeting only one type of host cell receptor.

The team observed that the strains circulating during the years of frequent outbreaks could use multiple receptors that are expressed on brain cells of humans and horses, including proteins known as PCDH10 and VLDLR.

Although the virus still circulates between birds, mosquitoes, and other animals, the most recent outbreak in the United States in humans was in 1987, according to the Centers for Disease Control and Prevention. Since then, there have been only five cases identified in the United States.

By contrast, when the researchers tested more recently isolated strains recovered from mosquitos in California in 2005, they found that the viral spike protein failed to recognize the human receptors, but could still interact with similar proteins found in birds.

Based on these findings, the researchers hypothesize that the virus had evolved, perhaps because horses can be vaccinated and are no longer prevalent enough in the agriculture or transportation industries to serve as effective amplifiers for the virus. Alternatively, the researchers note, the virus may have evolved through simple antigenic drifting, a process by which random mutations cause a series of small changes to a viral genome that, over time, may end up changing the way a virus interacts with its host. Whatever the reason, the researchers said, subtle shifts in the shape of the viral spike proteins changed the cellular receptors with which the virus could connect.

This change in targetable host receptors is likely the central reason why the virus “submerged” as a human pathogen in North America, the research team said. This newly gleaned appreciation of the dynamic complexity of viral receptors is an essential tool for understanding how this virus or others like it might one day re-emerge, the scientists said.

We need to understand what happens to viruses when they submerge, to better prepare for when they re-emerge.

Wanyu Li, first author
Kenneth C. Griffin Graduate School of Arts and Sciences
Harvard Division of Medical Sciences Harvard Medical School, Boston, MA, USA.

For example, knowing whether dangerous versions of the pathogen persist in isolated populations of insects, or if the virus has gained the ability to infect other animals, could provide important early warning signs for potential resurgences of illnesses that are thought to have disappeared.

A virus’s complex behavior

Through their experiments, the researchers discovered that certain old WEEV strains behaved differently than expected.

The team used eastern equine encephalitis virus—a deadlier cousin of WEEV—as a control in some experiments. In one test, the team found that an old strain of WEEV could use the same receptor as the eastern virus, which is something that newer WEEV strains could not do. They also found different strains of WEEV that used different receptors. Some strains could stick to avian versions of the receptor protein but not those expressed in human or equine cells.

The findings serve as an important reminder that viruses are part of a dynamic system and that the viruses themselves are dynamic, with subtle but significant differences across time and geography—a notion that was powerfully underscored by the rapidly shapeshifting SARS-CoV-2 virus that fueled the COVID-19 pandemic, the researchers said.

It was a wake-up call. It’s telling us that we can’t just study one strain of a virus and assume we know the whole story. Viruses seem simple, but they’re quite complex, and they’re constantly changing.

“There’s so much more biology to be learned by exploring the diversity of these complex systems.

Associate Professor Jonathan Abraham.

Applying lessons to pandemic preparedness

In standard virology, researchers often only check a limited number of viral strains. These new findings show that that’s not enough to truly understand the virus.

[Abraham] also noted that it’s necessary to explore as much of that viral diversity as possible in order to prepare for possible outbreaks.

Many viruses circulate in insects and animals that live around us, Abraham said. Some, like the tick-borne infection Powassan, which is endemic in New England, occasionally flare up to cause deadly or debilitating disease.

There could be many reasons for the flare-ups, Abraham said. Are there different strains of Powassan that carry different levels of risk? Is it an environmental change or an evolutionary shift in the pathogen itself that causes new outbreaks? Looking at all these aspects and the breadth of viral diversity will help researchers predict and protect against outbreaks.

In another twist, as Abraham and his team conducted their experiments, a new outbreak of WEEV occurred in South America, which had also seen steep declines in the disease in recent years. The viral populations in South and North America appear to be genetically distinct, and the South American strain of the virus doesn’t remain viable long enough for migrating birds to transfer it from one continent to the other regularly. Still, Abraham noted, the new outbreak in South America emphasizes the importance of vigilance and of improving scientific understanding of these volatile, shapeshifting viruses.

WEEV's return caught everyone by surprise. Now with its cellular host receptors known, we have the tools to understand the molecular aspects of WEEV's re-emergence.

Wanyu Li.

Abraham and collaborators are now investigating the strains associated with recent outbreak in South America.

One small shift in the viral genome, in the intensity of a rainy season that allows mosquitos to proliferate, or in the place humans live or work, could trigger an outbreak. The more we know, the better we’ll be able to protect ourselves.

Associate Professor Jonathan Abraham.

Abstract
Western equine encephalitis virus (WEEV) is an arthropod-borne virus (arbovirus) that frequently caused major outbreaks of encephalitis in humans and horses in the early twentieth century, but the frequency of outbreaks has since decreased markedly, and strains of this alphavirus isolated in the past two decades are less virulent in mammals than strains isolated in the 1930s and 1940s^1,2,3. The basis for this phenotypic change in WEEV strains and coincident decrease in epizootic activity (known as viral submergence3) is unclear, as is the possibility of re-emergence of highly virulent strains. Here we identify protocadherin 10 (PCDH10) as a cellular receptor for WEEV. We show that multiple highly virulent ancestral WEEV strains isolated in the 1930s and 1940s, in addition to binding human PCDH10, could also bind very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), which are recognized by another encephalitic alphavirus as receptors⁴. However, whereas most of the WEEV strains that we examined bind to PCDH10, a contemporary strain has lost the ability to recognize mammalian PCDH10 while retaining the ability to bind avian receptors, suggesting WEEV adaptation to a main reservoir host during enzootic circulation. PCDH10 supports WEEV E2–E1 glycoprotein-mediated infection of primary mouse cortical neurons, and administration of a soluble form of PCDH10 protects mice from lethal WEEV challenge. Our results have implications for the development of medical countermeasures and for risk assessment for re-emerging WEEV strains.

Main
Alphaviruses can cause devastating outbreaks of encephalitis in humans and equids. Examples include WEEV, eastern equine encephalitis virus (EEEV) and Venezuelan equine encephalitis virus^5,6,7 (VEEV). The transmission cycle of WEEV involves avian reservoir and amplification hosts and mosquitoes. Humans and horses are affected through the bite of infected mosquitoes. Manifestations of human WEEV infection range from mild or asymptomatic illness to encephalitis, with a case fatality rate as high as 50% in children below one year of age^5,6,8. Encephalitis can result in permanent neurological sequelae, including seizures, paralysis and intellectual disability6. No vaccines or antivirals have been approved by the US Food and Drug Administration for use against WEEV.

WEEV was first isolated during a 1930 outbreak in San Joaquin Valley, California that resulted in around 6,000 cases of encephalitis in horses7. The most severe WEEV epidemic occurred in 1941, with more than 3,000 reported human cases⁹. Since the middle of the twentieth century, WEEV outbreaks in humans and equids have markedly declined in frequency and scale^3,9. Fewer than 700 human cases were documented between 1964 and 2009 in the USA, and seroprevalence in residents of endemic regions in California decreased from 34% in 1960 to less than 3% in 19957. Surveillance of WEEV in birds and mosquitoes also detected a decline in circulation¹⁰.

Furthermore, the apparent reduction in epizootic infections and enzootic circulation has been accompanied by a decrease in the mammalian virulence of contemporary WEEV strains. Strains isolated in the 1930s and 1940s are more virulent in mouse models and lead to more rapid death than strains isolated later in the century, and a strain isolated in 2005 was shown to be nonpathogenic in mice and Syrian hamsters^2,11.

In South America, WEEV appeared to decline in a similar manner, with the last major outbreak occurring in 1988 in Argentina¹², although sporadic spillover events have occurred since^13,14. However, WEEV re-emerged in Argentina and Uruguay in November 2023, with more than 2,400 equid cases (clinically diagnosed and laboratory confirmed), 103 human cases and 10 human fatalities as of 31 March 2024^12,15,16,17. The molecular determinants of WEEV infectivity in mammalian cells remain unknown, as do factors that drive the marked phenotypic change in WEEV strains isolated over the past century. A better understanding of determinants of WEEV infection of mammalian cells is urgently needed for risk assessment of re-emerging strains and to facilitate outbreak preparedness.

There is a simple choice here for creationists. Is this a case of evolution, of incompetent design, or a trick to lull us into a false sense of security?

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