Headspace Invaders: How Mosquito-Borne Viruses Breach the Brain’s Defenses

Mosquito-borne viruses can cause more than fevers and joint pain. In severe cases, they invade the brain, leading to seizures, encephalitis, lasting memory loss, and sometimes death. But thanks to a new UCLA study, Melody’s Li lab has uncovered how some of these viruses breach the brain’s defenses — and point toward ways of keeping them out.

This research, published in Cell Reports, focuses on Sindbis virus, a relatively mild pathogen that scientists use as a safe stand-in for more dangerous mosquito-borne viruses such as chikungunya. 

The team discovered that the invasive strain grips just one or two specific proteins on blood-brain barrier cells, turning those proteins into doorways that let the virus inside. By contrast, the non-invasive strain spreads its efforts across many receptors and is far less successful. “What surprised us most was that the invasive strain narrows its focus,” said Pablo Alvarez, first author of the study and a graduate student in the lab of senior author Dr. Li. “It doesn’t try every option — it specializes, and that makes it much more effective.”

Looking ahead, the researchers plan to investigate additional alphaviruses and to drill down on the exact atomic-level interactions between viral glycoproteins and host receptors. Such insights could guide the development of therapies that prevent the virus from entering the brain or inform the engineering of weakened viral strains for use as vaccines. “This is really just the beginning,” Li said. “By improving our models and expanding our studies, we hope to stay ahead of these emerging pathogens.”

This research was funded by a UCLA Broad Stem Cell Research Center Research Award, BSCRC Rose Hills Foundation Innovator Award, a David Geffen School of Medicine W.M. Keck Foundation Junior Faculty Award, a Jonsson Comprehensive Cancer Center-BSCRC Ablon Scholars Award and the National Institutes of Health.