Researchers at the University of Colorado in the United States have revealed why chikungunya virus infection turns into a chronic disease in about half of those infected, after years of not understanding this phenomenon.
The mosquito-borne virus that causes high fever, inflammation, and severe joint pain has recently returned to spread strongly in many countries around the world.
In the first nine months of 2025 alone, the World Health Organization reported more than 445,000 cases and 155 deaths in 40 countries.
The major problem is that about half of those infected develop the disease into a chronic form, where they suffer from recurrent joint pain and inflammation that may last for years, and there is no cure for this condition yet.
But a research team led by scientist Thomas Morrison, professor of immunology and microbiology at the University of Colorado Anschutz, has finally been able to understand the mechanism that makes the virus stay in the body for long periods.
In a new study published in the journal Nature Microbiology, researchers explained that the chikungunya virus hides inside a specialized type of white blood cell called macrophages. These cells are found in the tissues surrounding the joints and normally protect the body from pathogens. However, the virus uses them as a "safe haven" that protects it from the immune system, allowing it to remain active for extended periods and cause inflammation and chronic pain.
Prior to this study, scientists were unsure why the pain persisted. Some believed the virus triggered a faulty immune response that caused the body to attack itself, as occurs in autoimmune diseases like rheumatoid arthritis. However, the evidence for this theory remained inconclusive.
The other hypothesis, which Morrison’s team proved, says that the viral infection itself lasts for long periods, as the immune response fails to completely eliminate the virus from some tissues, specifically tissues associated with the joints.
To discover this, the researchers used very advanced techniques, including single-cell RNA sequencing and spatial gene expression analysis, techniques that allow mapping gene activity within joint tissues and identifying which cells specifically harbor the virus.
Thanks to the development of small-molecule antiviral drugs capable of stopping viral replication, the team was able to prove that phagocytic cells do indeed provide a safe haven for the virus.
In an important step towards treatment, researchers used these antiviral drugs in trials and found that they reduce chronic viral RNA and alleviate inflammation in the joints.
This means that targeting the virus itself, rather than just alleviating symptoms, may be the key to treating patients with chronic pain.
The implications of this discovery are significant, particularly in impoverished areas of the world where the virus is spreading. Many people there rely on manual labor for their livelihood, and developing chronic joint pain could mean losing their source of income.
The new understanding also opens the door to the development of antiviral treatments that could prevent the disease from progressing to its chronic stage, or even treat existing chronic conditions.
Morrison says his team is now focusing on two new questions: How does the virus manage to survive inside phagocytic cells? And why do these cells become a safe reservoir for the virus instead of destroying it as expected? But most importantly, the researcher emphasizes, the current findings clearly indicate that "persistent viral infection may be at the root of chronic disease symptoms," and that antiviral treatment offers real hope for millions of patients worldwide.
