For most people infected with Chikungunya virus (CHIKV), the illness is over in a few weeks, marked by a febrile illness, rash, and joint and muscle pain. But for as many as 60% of patients, the virus leaves behind a far more persistent symptom: incapacitating joint pain, called arthralgia, that mimics autoimmune conditions like rheumatoid arthritis and can last for months or years.
In a new study published in Cell Reports Medicine titled, “Chikungunya virus-specific CD4+ T cells are associated with chronic chikungunya viral arthritic disease in humans,” scientists at La Jolla Institute for Immunology (LJI) offer the first detailed look at how the body’s T cells respond to CHIKV—and how this immune response may underlie long-term symptoms of Chikungunya virus disease (CHIKVD).
“Autoimmune diseases like rheumatoid arthritis have exactly these parameters,” said Daniela Weiskopf, PhD, senior author of the study and assistant professor at LJI’s Center for Vaccine Innovation.
To investigate the immune mechanisms behind CHIKVD, the researchers collected peripheral blood mononuclear cells (PBMCs) from 39 individuals in Colombia who were infected during the 2014–2015 CHIKV epidemic. They used overlapping peptide pools spanning the entire CHIKV proteome to stimulate immune cells and assess T cell activation using flow cytometry and cytokine staining assays.
The study revealed robust CHIKV-specific CD4+ T cell responses, particularly in individuals with chronic arthralgia. These patients showed higher CD4+ T cell reactivity against nonstructural proteins nsP1 and nsP2 and the E2 structural protein. In contrast, CD8+ T cell responses were rare.
Critically, individuals with chronic symptoms also exhibited a significantly lower frequency of Th1 CD4+ T cells and had CD4+ T cells that predominantly produced tumor necrosis factor alpha (TNF-α), an inflammatory cytokine, “…over 94% of symptomatic individuals produced TNF-⍺ in response to CHIKV proteins.” Meanwhile, recovered individuals’ T cells more frequently produced interferon gamma (IFN-γ), a broader immune signal.
“There are many studies in mice showing that CD4+ T cells are pathogenic,” said Rimjhim Agarwal, co–first author and graduate student at UC San Diego. “So we needed to know what CD4+ T cells are doing in people with CHIKV.”
The findings provide a plausible explanation for why some people continue to suffer joint pain long after the virus has been cleared. No viral RNA or proteins were detected in human patients nearly two years post-infection. Instead, the researchers found that 87% of patients still had CHIKV-specific memory CD4+ T cells almost six years after diagnosis.
This CD4+ T cell profile, characterized by monofunctionality and TNF-α production, bears resemblance to immune patterns seen in autoimmune disease.
“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,” said Agarwal. “We still have a lot more questions than answers right now, but we want to understand the relationship between viruses and autoimmune diseases.”
With further study, these insights could help inform treatment strategies, such as therapies that block the harmful inflammation and alleviate arthritis-like symptoms in CHIKV patients.
The post T Cell Memory May Explain Chikungunya-Linked Chronic Pain appeared first on GEN - Genetic Engineering and Biotechnology News.
In a new study published in Cell Reports Medicine titled, “Chikungunya virus-specific CD4+ T cells are associated with chronic chikungunya viral arthritic disease in humans,” scientists at La Jolla Institute for Immunology (LJI) offer the first detailed look at how the body’s T cells respond to CHIKV—and how this immune response may underlie long-term symptoms of Chikungunya virus disease (CHIKVD).
“Autoimmune diseases like rheumatoid arthritis have exactly these parameters,” said Daniela Weiskopf, PhD, senior author of the study and assistant professor at LJI’s Center for Vaccine Innovation.
Mapping the immune response
To investigate the immune mechanisms behind CHIKVD, the researchers collected peripheral blood mononuclear cells (PBMCs) from 39 individuals in Colombia who were infected during the 2014–2015 CHIKV epidemic. They used overlapping peptide pools spanning the entire CHIKV proteome to stimulate immune cells and assess T cell activation using flow cytometry and cytokine staining assays.
The study revealed robust CHIKV-specific CD4+ T cell responses, particularly in individuals with chronic arthralgia. These patients showed higher CD4+ T cell reactivity against nonstructural proteins nsP1 and nsP2 and the E2 structural protein. In contrast, CD8+ T cell responses were rare.
Critically, individuals with chronic symptoms also exhibited a significantly lower frequency of Th1 CD4+ T cells and had CD4+ T cells that predominantly produced tumor necrosis factor alpha (TNF-α), an inflammatory cytokine, “…over 94% of symptomatic individuals produced TNF-⍺ in response to CHIKV proteins.” Meanwhile, recovered individuals’ T cells more frequently produced interferon gamma (IFN-γ), a broader immune signal.
“There are many studies in mice showing that CD4+ T cells are pathogenic,” said Rimjhim Agarwal, co–first author and graduate student at UC San Diego. “So we needed to know what CD4+ T cells are doing in people with CHIKV.”
Future directions and viral connections
The findings provide a plausible explanation for why some people continue to suffer joint pain long after the virus has been cleared. No viral RNA or proteins were detected in human patients nearly two years post-infection. Instead, the researchers found that 87% of patients still had CHIKV-specific memory CD4+ T cells almost six years after diagnosis.
This CD4+ T cell profile, characterized by monofunctionality and TNF-α production, bears resemblance to immune patterns seen in autoimmune disease.
“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,” said Agarwal. “We still have a lot more questions than answers right now, but we want to understand the relationship between viruses and autoimmune diseases.”
With further study, these insights could help inform treatment strategies, such as therapies that block the harmful inflammation and alleviate arthritis-like symptoms in CHIKV patients.
The post T Cell Memory May Explain Chikungunya-Linked Chronic Pain appeared first on GEN - Genetic Engineering and Biotechnology News.