Healthcare (Commonwealth Union) – Mosquito-transmitted viruses can do more than trigger fevers and joint pain. In serious cases, they can penetrate the brain, causing seizures, encephalitis, permanent memory loss, and sometimes death. A new study from the University of California, Los Angels (UCLA), however, has revealed how certain viruses manage to bypass the brain’s defenses — and hints at strategies to prevent this.
Published in Cell Reports, the research centers on the Sindbis virus, a relatively mild pathogen that scientists often use as a safe stand-in for more dangerous mosquito-borne viruses like chikungunya.
Using a stem cell-based model of the human blood-brain barrier, created in collaboration with Florida State University, the UCLA researchers examined two closely related strains of Sindbis — one capable of invading the brain and one not. They found that tiny differences in viral surface proteins, known as glycoproteins, determine whether the virus can cross into the brain.
The findings demonstrated that the brain-invading strain targets just one or two precise proteins on blood-brain barrier cells, effectively turning them into opening points. The non-invasive strain, on the other hand, interacts with multiple receptors and is far less effective at breaching the barrier.
“What surprised us most was that the invasive strain narrows its focus,” explained Pablo Alvarez, the first author of the study. “It doesn’t try every option — it specializes, and that makes it much more effective.”
To see if the trend applied beyond Sindbis, the team examined chikungunya, a virus responsible for large outbreaks around the globe. They discovered that the virulent strain of chikungunya was far more effective at invading blood-brain barrier cells compared to a milder strain that does not lead to serious disease.
Overall, the findings indicate that infecting blood-brain barrier cells may be a shared trait among alphaviruses that spread to the brain, even though each virus might employ distinct tactics. By mapping out the viral glycoproteins and the host proteins they latch onto, the research points to valuable molecular targets for developing vaccines and antiviral therapies.
Li, who is an associate professor of microbiology, immunology and molecular genetics and member of the UCLA Broad Stem Cell Research Center pointed out that recognizing this interaction between viral proteins and the brain’s blood vessels gives them a precise target.
She further indicated that if they can block that link, they may be able to halt the infection before it penetrates the brain.
Researchers of the study indicated that although Sindbis is not considered a serious threat to people, its relatives in the alphavirus family are far more dangerous. In the United States, Eastern equine encephalitis virus is already present along the East Coast and has triggered health warnings, since brain infections from it are frequently deadly.
The researchers further pointed out that chikungunya, now circulating in over 100 countries, has also been linked to outbreaks with severe effects on the nervous system. With global travel and climate change helping mosquitoes spread into new territories, the chances of these viruses reaching fresh populations are on the rise.
“These viruses are already here, and climate change is only increasing the risk,” explained Alvarez. “By learning how they breach the brain’s defenses, we can identify their weak points — and that’s the first step toward protecting people from the most devastating outcomes.”
Going forward, the team intends to study other alphaviruses and examine in detail how viral glycoproteins interact with host cell receptors at the atomic scale. Understanding these mechanisms could pave the way for treatments that block the virus from crossing into the brain or support the design of weakened viral forms that serve as vaccines.
Li stated that this is only the starting point and by refining their models and broadening their research, they aim to stay one step ahead of these emerging threats.
