Rosa Rubicondior: Malevolent Or Incompetent Design?

The Aedes mosquito is the primary vector for the Chikungunya virus

LJI scientists uncover clues to how a viral infection can lead to arthritis-like disease – lji.org

Scientists believe they have uncovered a mechanism by which a viral infection can trigger a persistent autoimmune response, leading to chronic and often severe pain.

If fully understood, this discovery poses a significant challenge to Intelligent Design (ID) creationism. Under the ID paradigm, such an outcome leaves us with two unpalatable options: either the designer is incompetent, having failed to foresee the consequences of a poorly calibrated immune system, or the suffering inflicted on random individuals is intentional—engineered by design.

This finding also reignites a long-standing issue for creationism: the existence of parasites, particularly viruses. According to criteria promoted by Discovery Institute fellows William A. Dembski ("complex specified information") and Michael J. Behe ("irreducible complexity"), viruses must be regarded as the product of intelligent design. Yet these same entities are responsible for making us ill—seemingly by the same designer who supposedly crafted our immune system to protect us from them. The contradiction is striking.

The explanation stems from recent work by a research team at the La Jolla Institute for Immunology and is published in Cell Reports Medicine.

What information do you have on the Chikungunya virus? The Chikungunya virus (CHIKV) is an arthropod-borne virus (arbovirus) in the Togaviridae family, genus Alphavirus. It's primarily transmitted to humans by the bites of infected Aedes mosquitoes, notably Aedes aegypti and Aedes albopictusthe same vectors that transmit dengue and Zika viruses.

Key Characteristics:

Genome: Single-stranded, positive-sense RNA virus.
Structure: Enveloped, icosahedral capsid, \~60–70 nm in diameter.
Origin: First identified in Tanzania in 1952. The name “Chikungunya” comes from the Makonde language, meaning “to become contorted,” referencing the stooped posture of patients due to joint pain.

Transmission:

Primary vector: Aedes species mosquitoes.
Reservoirs: In Africa, a sylvatic cycle exists involving primates and forest mosquitoes. In Asia and the Americas, transmission is mostly human-mosquito-human.
Non-vector transmission: Rare, but possible through blood transfusion, organ transplant, or vertical transmission (mother to child during birth).

Symptoms:

Incubation period: 2–7 days after mosquito bite.
Acute symptoms (usually sudden onset):

High fever (often >39°C)
Severe joint pain (arthralgia), often debilitating and symmetric
Headache
Muscle pain
Rash
Fatigue

Chronic phase:

In some individuals, especially older adults or those with comorbidities, joint pain can persist for months or even years, resembling rheumatoid arthritis.

Diagnosis:

Clinical: Based on symptoms and travel history.
Laboratory:

RT-PCR during the viraemic phase
ELISA or PRNT for IgM and IgG antibodies (later stages)
Cross-reactivity with other arboviruses (e.g., dengue) can complicate diagnosis.

Treatment:

No specific antiviral exists.
Supportive care:

NSAIDs or paracetamol (avoid aspirin due to bleeding risk)
Hydration and rest
Corticosteroids for chronic inflammatory symptoms in select cases

Vaccine Status:

No licensed vaccine yet (as of 2024), but several candidates are in clinical trials.

Public Health Concerns:

Outbreaks:

Historically confined to Africa and Asia, but since 2004, CHIKV has caused significant global outbreaks, including in Europe and the Americas.
Notably, a mutation in the E1 gene increased the virus’s ability to be transmitted by Aedes albopictus, expanding its geographic range.

Climate change and urbanisation are facilitating the spread of mosquito vectors, increasing the virus’s global threat potential.

Relevance to Autoimmunity:

Recent research suggests Chikungunya virus can trigger long-term autoimmune-like conditions, especially chronic arthritis, by provoking a dysregulated immune response. The persistence of joint symptoms may be due to:

Viral RNA or proteins lingering in tissues
Molecular mimicry triggering autoimmunity
An imbalance in immune regulation following infection

This is relevant to discussions about the evolution (or poor design) of the immune system and how pathogens exploit or disrupt it.

A news release by the La Jolla Institute provides further details:

LJI scientists uncover clues to how a viral infection can lead to arthritis-like disease.
By studying Chikungunya virus, LJI scientists shed light on how immune responses to viral infections may lead to persistent symptoms of autoimmune disease.
LA JOLLA, CA—Chikungunya virus (CHIKV) is a mosquito-borne pathogen that has been identified in more than 110 countries around the world. The virus typically causes flu-like symptoms, but it can also trigger chronic, severe joint pain in some people.

Researchers at La Jolla Institute for Immunology (LJI) are working to understand how a viral infection can cause persistent joint pain that closely resembles rheumatoid arthritis, an autoimmune disease.

In a new study, LJI scientists share a critical first look at how the body’s T cells target CHIKV. Their research suggests CD4⁺ T cells step up to fight the virus—and cause chronic inflammation in the process. This discovery may help explain why some people infected with CHIKV develop severe joint pain.

Autoimmune diseases like rheumatoid arthritis have exactly these parameters.

Assistant Professor Daniela Weiskopf, Ph.D., senior author
Center for Vaccine Innovation
La Jolla Institute for Immunology (LJI), La Jolla, CA, USA.

The findings, published recently in Cell Reports Medicine, offer new clues to why some viral infections appear to trigger autoimmune disease. The research may also help guide the development of therapies to block harmful inflammation.

Testing immune cells vs. Chikungunya virus

Weiskopf and her colleagues studied immune cells found in blood samples from a group of CHIKV patients in Colombia. The researchers tested how immune cells from these patients responded to small molecular chains, called peptides, from Chikungunya virus.

This experiment revealed which types of immune cells take the lead in fighting CHIKV infection. The researchers also captured the first-ever look at which sites on CHIKV, called viral epitopes, drew the strongest immune cell responses.

To their surprise, the researchers found that a type of T cells called CD4⁺ T cells showed a strong response to CHIKV. Although CD4⁺ T cells are a normal part of the body’s anti-viral response, they are almost always accompanied by CD8⁺ T cells. Scientists have even nicknamed CD8⁺ T cells “killer” T cells because they play a very active role in fighting infections.

Yet the new study shows that CD4⁺ T cells are most active in fighting CHIKV virus. These same CD4⁺ T cells stay in the body as “memory” T cells after the infection is gone.

The researchers found that 87 percent of patients had detectable levels of CHIKV-specific memory CD4⁺ T cells in their blood six years after their initial infection. In contrast, only 13 percent of patients still had CHIKV-specific memory CD8⁺ T cells in their blood after six years.

According to Weiskopf, this kind of CD4⁺ T cell profile is more commonly seen in patients with autoimmune diseases.

I’m an infectious disease researcher, but I could see that this T-cell response looked awfully like what we see in autoimmune disease.

Assistant Professor Daniela Weiskopf, Ph.D,

Not your typical T cells

This CD4⁺ T cell activity may help explain the association between CHIKV infection and chronic, autoimmune-like disease.

There are many studies in mice showing that CD4⁺ T cells are pathogenic. So we needed to know what CD4⁺ T cells are doing in people with CHIKV.

Rimjhim Agarwal, first author
Center for Vaccine Innovation
La Jolla Institute for Immunology (LJI), La Jolla, CA, USA.

The researchers took a closer look exactly how CD4⁺ T cells fought CHIKV infection. Normally, CD4⁺ T cells are “polyfunctional,” meaning the cells can churn out many kinds of signalling molecules to help coordinate the body’s immune response to a pathogen.

But CHIKV patients who developed severe joint pain had more “monofunctional” CD4⁺ T cells. Even years after initial infection, their T cells primarily produced an inflammatory molecule called TNF-alpha. This molecule helps direct immune cell activity during an infection, but TNF-alpha is not supposed to linger long after a virus has been cleared.

The new study offers evidence that these monofunctional CD4⁺ T cells may be the culprits behind joint pain and chronic inflammation following CHIKV infection. Although there’s still a lot to learn, the researchers say future therapies that inhibit TNF-alpha may hold promise for treating arthritis-like symptoms in CHIKV patients.

Next steps for helping patients

The new study raises many big questions. Agarwal is currently working to explain a strange phenomenon—why are women in their forties much more likely to develop chronic joint pain following CHIKV infection?

Last year, Agarwal won funding through LJI’s Tullie and Rickey Families SPARK Awards for Innovations in Immunology to investigate this sex-based difference. Her SPARK project, specifically funded by the Rosemary Kraemer Raitt Foundation Trust, may help shed light on whether CD4⁺ T cells are mistakenly attacking the body’s own tissues when responding to CHIKV.

This work comes as more scientists today look at possible connections between viral infections and autoimmune disease. Other viruses, such as the mosquito-borne dengue virus, can also cause severe, chronic joint pain. Many people today are also dealing with “long COVID,” chronic and debilitating autoimmune-like inflammation that often follows SARS-CoV-2 infection.

More and more people are realizing, particularly after seeing the long-term effects of SARS-CoV-2, that viral infection can trigger autoimmune-like disease. We still have a lot more questions than answers right now, but we want to understand the relationship between viruses and autoimmune diseases.

Rimjhim Agarwal

Additional authors of the study, “Chikungunya virus-specific CD4⁺ T cells are associated with chronic chikungunya viral arthritic disease in humans,” were James Chang, Fernanda H Côrtes, Calvin Ha, John Villalpando, Izabella N. Castillo, Rosa Isela Gálvez, Alba Grifoni, Alessandro Sette1,5 6 , Claudia M. RomeroVivas, Mark T Heise, Lakshmanane Premkumar, and Andrew K Falconar.

Publication:
Agarwal, Rimjhim; Chang, James; Côrtes, Fernanda H.; Ha, Calvin; Villalpando, John; Castillo, Izabella N.; Gálvez, Rosa Isela; Grifoni, Alba; Sette, Alessandro; Romero-Vivas, Claudia M.; Heise, Mark T.; Premkumar, Lakshmanane; Falconar, Andrew K.; Weiskopf, Daniela
Chikungunya virus-specific CD4⁺ T cells are associated with chronic chikungunya viral arthritic disease in humans
Cell Reports Medicine (2015); DOI: 10.1016/j.xcrm.2025.102134

Immune Matters Magazine article: For some women, one mosquito bite leads to chronic pain.

Highlights

Frequency of CHIKV-specific CD4⁺ T cells is higher in chronic CHIKV disease
nsP1, E2, and E1 are immunodominant
CHIKV-specific CD4⁺ T cells primarily produce TNF-⍺ in chronic CHIKV disease

Summary
Chikungunya virus (CHIKV) is a mosquito-borne virus that can cause chronic chikungunya virus disease (CHIKVD), which is characterized by persistent incapacitating arthralgia. Despite recurring CHIKV outbreaks and recent approval of a vaccine, the breadth and target of T cell responses in CHIKVD remain largely understudied. Here, we tested peripheral blood mononuclear cells (PBMCs) collected from CHIKV-infected individuals against overlapping peptide pools sequentially spanning the entire CHIKV proteome. We detected robust CHIKV-specific CD4⁺, but not CD8⁺, T cell responses in infected individuals. Individuals with chronic arthralgia displayed significantly higher CD4⁺ T cell responses against nsP1, nsP2, and E2 proteins and exhibited a significantly lower Th1 CD4⁺ T cell population, compared to individuals who had recovered. Additionally, CD4⁺ T cells in chronic individuals were marked by a predominant production of tumor necrosis factor alpha (TNF-α). Overall, our work comprehensively characterizes T cell responses in CHIKVD in humans and provides insights into the role of T cells in CHIKVD.
Graphical abstract

Introduction
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus in the family Togaviridae. The viral genome consists of two open-reading frames and encodes four non-structural proteins (nsP1–4) responsible for the viral replication machinery and five structural proteins (Capsid [CP], E3, E2, 6K, and E1).¹ The capsid proteins form the viral core that encapsulates the genomic RNA, while the E2 and E1 proteins play a pivotal role in facilitating viral assembly.²

First identified in Tanzania in 1952,³ CHIKV led to recurrent outbreaks in tropical and sub-tropical regions worldwide, before causing a major outbreak in 2005–2006 in La Réunion Island, where almost a third of the population was infected.^4,5,6 Subsequently in 2014–2015, CHIKV spread to the Americas and caused a huge epidemic in Central and South America.7 The spread of CHIKV has been facilitated by the expanding geographic range of Aedes mosquitoes, posing a significant public health concern.^7,8 In 2023, there were over 500,000 cases and over 400 deaths reported from CHIKV globally.⁹

The acute phase of CHIKV infection is characterized by the sudden onset of febrile illness, maculopapular rash, and joint and muscle pain. Although the majority of infected individuals fully recover within 7–14 days, an estimated 30%–60% of them experience incapacitating arthralgia, primarily affecting small joints, which can persist for months to years post-infection.^{10,11,12,13,14,15} Current therapeutic approaches primarily involve non-steroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs; however, the efficacy of the treatment greatly varies between individuals.¹⁶ A live-attenuated single-shot CHIKV vaccine, VLA1553, was recently approved by the US Food and Drug Administration after showing very high seroresponse rate in participants in phase 3 clinical trials.¹⁷

At present, the underlying mechanisms responsible for the development of chronic arthralgia symptoms remain elusive. In adult mice, CHIKV RNA could be detected 60–90 days post-infection in joint tissues¹⁸ and for weeks after infection in the joints, muscle, and lymphoid tissue of rhesus macaques.^15,19 However, a comprehensive analysis of synovial fluid via quantitative reverse-transcription PCR (RT-qPCR) and mass spectrometry in 38 human patients showed no evidence of viral RNA or proteins 22 months post-infection.²⁰ Multiple animal^15,21,22,23 and human studies^24,25 have revealed that joints are commonly infiltrated with macrophages and T cells, suggesting that chronic chikungunya virus disease (CHIKVD) is immune mediated.

T cells play a pivotal role in combating viral infections. The targets of T cells and their possible role in CHIKV pathogenesis are not adequately investigated. A recent study suggests CHIKV can establish persistent infection in mice by evading CD8⁺ T cell responses23 by disrupting major histocompatibility complex class I expression through the nsP2 protein.²⁶ Other studies have shown that CD4⁺ T cells are the primary mediators of joint inflammation and swelling in mice, which can be treated by suppressing T cell responses.^27,28 However, few studies have been performed to elucidate the function of T cells during the chronic phase of CHIKVD in humans. As such, one study reported the presence of CHIKV-specific T cells one–two years after the La Réunion outbreak, but no difference was observed in patients still experiencing chronic disease compared to patients who resolved the disease.²⁹ However, since symptoms can persist for longer durations, it is essential to determine the involvement of T cells in the late chronic stages of the disease.

Here, using an ex vivo T cell stimulation assay, we show that CD4⁺ T cells are associated with chronic CHIKVD in humans. Peripheral blood mononuclear cells (PBMCs) were collected from individuals infected during the 2014–2015 CHIKV epidemic in Colombia and were stimulated with CHIKV-specific peptide megapools (MPs) that sequentially spanned the entire CHIKV proteome. The magnitude and functionality of CHIKV-specific CD4⁺ and CD8⁺ T cells were determined in an activation-induced marker (AIM) and intracellular cytokine staining assay, respectively. Interestingly, we found that chronic individuals have a significantly higher percentage of CHIKV-specific memory CD4⁺ T cells almost six years post-infection compared to recovered individuals, while CD8⁺ T cells were hardly detected in either group. Most CD4⁺ T cell responses in chronic individuals were directed against nsP1, nsP2, and E2 proteins and exhibited significantly lower frequency of Th1 cells. Additionally, the majority of CHIKV-specific CD4⁺ T cells produced a single cytokine, with tumor necrosis factor alpha (TNF-α) being the most highly produced cytokine in the chronic group and interferon (IFN)-γ being the most highly produced in the recovered group. Overall, our work expands the current understanding of the pathogenesis of chronic CHIKVD and provides an insight into possible therapeutic options.

Agarwal, Rimjhim; Chang, James; Côrtes, Fernanda H.; Ha, Calvin; Villalpando, John; Castillo, Izabella N.; Gálvez, Rosa Isela; Grifoni, Alba; Sette, Alessandro; Romero-Vivas, Claudia M.; Heise, Mark T.; Premkumar, Lakshmanane; Falconar, Andrew K.; Weiskopf, Daniela
Chikungunya virus-specific CD4⁺ T cells are associated with chronic chikungunya viral arthritic disease in humans
Cell Reports Medicine (2015); DOI: 10.1016/j.xcrm.2025.102134

Copyright: © 2025 The authors.
Published by Elsevier Inc. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

The recent discovery that viral infections—such as those caused by the Chikungunya virus—can lead to long-term autoimmune disorders, including chronic pain and arthritis-like symptoms, poses a fundamental problem for creationist claims, particularly those rooted in Intelligent Design (ID). According to ID proponents, biological systems exhibit hallmarks of purposeful engineering by a benevolent, intelligent agent. Yet the idea that a virus could trigger the body to attack itself, resulting in prolonged suffering for no apparent reason, is difficult to reconcile with the notion of an all-wise, compassionate designer. Either the designer is incompetent, having failed to anticipate such a malfunction, or it is malevolent, deliberately engineering a system in which viruses not only evade immune defences but also redirect them against the host.

Furthermore, ID theorists like William Dembski and Michael Behe have argued that features such as the immune system and viral machinery exhibit “complex specified information” and “irreducible complexity,” respectively—terms intended to demonstrate intelligent origin. But if both the immune system and the viruses that exploit and undermine it are intelligently designed, then the design is incoherent at best and cruel at worst. Why would a designer create a defence system so vulnerable to subversion by other elements of its own creation?

In contrast, the theory of evolution by natural selection offers a coherent and well-evidenced explanation. It recognises that the immune system, like all biological traits, is the product of cumulative adaptations shaped by environmental pressures, historical constraints, and random mutation. There is no foresight in evolution—only the immediate reproductive success of each variation. Pathogens evolve mechanisms to exploit hosts, and hosts evolve countermeasures, resulting in an evolutionary arms race. Autoimmunity can be understood as a byproduct of this imperfect and ongoing struggle: a defence system honed to detect danger sometimes misfires, especially when pathogens mimic host molecules or provoke hyperactive responses. What appears as poor design is, in fact, the expected outcome of natural processes working without intent, purpose, or guarantee of optimal outcomes.

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