Imagine your body as a building with layered security: locked doors, sealed windows, and guards. Most “stomach bugs” never make it past the lobby. But some of the newer strains of Human Astrovirus seem to do something far more unsettling. They slip past the body’s security system and show up in restricted areas like the lungs and even the brain.
Human Astrovirus (HAstV) is a tiny yet widespread virus that is best known for causing stomach flu, especially in infants, the elderly, and those with weakened immune systems. Traditionally, this virus stays in the gut, where it can cause symptoms like diarrhea, dehydration, and stomach cramps. But in recent years, scientists have discovered something concerning: new versions of this virus can travel far beyond the digestive system, reaching places like the brain and lungs, where they might contribute to serious conditions such as inflammation of the brain’s protective membranes (meninges) or the brain tissue itself.
A summer research project by Finn Coughlin in the Biering Lab at UC San Diego aimed to understand how these genetically distinct versions of the virus — known as the MLB and VA clades — are able to spread to organs that the original strain could not. His work suggests that the virus uses the small protruding structures on the virus’s surface, known as “spike proteins”, to weaken the protective barriers that usually keep harmful substances out of the bloodstream, lungs, and brain.
Finn has been interested in virology since before the COVID-19 pandemic. “Something so neat and microscopic can affect your whole body,” he said. “It’s spooky.” Human astrovirus stood out to him because it isn’t just common, it’s unpredictable. “There are niche cases with crazy effects,” he explained. In a world that has seen how quickly a virus can reshape everyday life, studying these “unknowns” is not just academic curiosity; it’s preparation for identifying, tracking, and preventing future viral threats.
To understand what Finn was investigating, it helps to picture the body like a building with multiple layers of security. One of the most important protective layers is the endothelium, a thin sheet of cells that lines blood vessels and acts as a gatekeeper between the blood and surrounding tissues. Endothelial cells are tightly connected and coated with a sugar-rich shield called the endothelial glycocalyx layer (EGL). Think of the EGL as a fuzzy protective coat made of molecules like sialic acid and heparan sulfate that cushions blood vessels and helps keep them sealed. Together with protein “seals” between cells, this coat controls what enters the bloodstream and what stays out. Earlier studies have shown that some viruses can break down the EGL, making the blood vessel walls “leaky” and easier to cross. Finn’s research asked whether the new astrovirus spike proteins also damage this protective layer, and if so, whether different versions of the virus target different organs.
To test that idea, Finn conducted a “stress test” for the body’s security system by focusing on one key “tool” the virus carries: its spike proteins. Finn used human cells that mimic the lining of lung blood vessels and brain blood vessels grown in laboratory dishes. He exposed these cells to purified spike proteins from (1) Classical HAstV strains, which are limited to the gut, (2) Novel strains MLB1, MLB2, and VA1, and (3) known controls, including enzymes and virus proteins that specifically break down EGL components and endothelial barriers. Using a technique called immunofluorescence —a method that uses glowing dyes to track specific molecules — he stained the protective molecules on the EGL so they would glow under a microscope. If the signal weakened, it meant the spike protein had degraded that part of the protective layer. He then measured the brightness of each signal using the software ImageJ, which allowed him to calculate mean fluorescence intensity (MFI), a numerical way to measure how much of a molecule remains. Lower brightness meant more damage.
The next step was to see what kind of damage each clade — genetically distinct group of the virus — could cause in different endothelial cell types. Since sialic acid is a key component of the EGL’s protective “coat”, Finn first looked at whether the spike proteins were stripping away this crucial layer. When he tested lung endothelial cells, he found that the MLB1 spike protein caused a clear drop in sialic acid. Surprisingly, classical strain HAvstV-1 also reduced sialic acid, suggesting that it may be more versatile than previously thought. VA1, another novel strain, did not degrade lung sialic acid. This suggests that MLB viruses may be particularly good at breaking into the lungs, and could explain why MLB strains are sometimes detected outside the gut. But the lungs are only half the story. In brain endothelial cells, the pattern reversed: the VA1 spike protein caused strong degradation of sialic acid, whereas MLB1 did not degrade sialic acid in the brain. These results match clinical observations that VA clades are more often associated with brain infections.
Ultimately, the MLB clade showed stronger effects in lung endothelial cells, while the VA clade showed stronger effects in brain endothelial cells. For Finn, this was the moment the results “clicked”. He described it as a “lock and key” situation where certain viral spikes may interact best with certain tissues. Both novel strains may damage another key molecule, heparan sulfate — a proteoglycan (or sugar-protein) — that helps maintain endothelial barrier integrity. Finn’s preliminary results show that both VA1 and MLB1 reduced heparan sulfate levels in brain endothelial cells. Some of the data was inconclusive due to technical issues such as uneven cell growth. Additionally, the limited number of replicates prevented definitive conclusions, and more trials are needed to confirm this part of the story.
Finn’s research helps explain why the new astrovirus strains are more dangerous. By breaking down the EGL, the virus weakens a major protective barrier of the blood vessels that normally prevent viruses from spreading throughout the body. Although the MLB and VA clades were first identified in different parts of the world, their geographic origins are less important than the genetic differences that separate them, differences that may explain why each strain targets distinct organs. Each novel strain seems to specialize in a different organ system: the MLB clade primarily affects lung endothelial cells, whereas the VA clade primarily affects brain endothelial cells. This also expands our understanding of how viruses move through the body. Instead of infecting cells directly, they may use spike proteins to bypass the body’s barriers, allowing them to spread more easily.
That idea matters in a world where we’ve already seen how quickly an emerging virus can disrupt global health systems. Finn connected this to the importance of being proactive. “It’s always relevant to be ahead of the curve,” he said, especially given the fear of zoonotic spillover, where viruses jump from animals to humans. He frames it as an “arms race,” taking from a phrase he heard from Virology Professor Alistair Russell: “An arm is raised.” In other words, as science advances, pathogens adapt, so research must keep pace.
Like any good research project, Finn’s work also revealed areas that warrant further investigation. Heparan sulfate data from lung endothelial cells were not reliable enough to interpret, emphasizing the need for further validation. Additionally, because this study focused only on endothelial cells, it remains unclear how these spike proteins affect the gut, where astrovirus infections typically begin. To understand the classic gut symptoms of human astrovirus, the next step is to test the spike proteins on gut epithelial cells. Future research will help determine whether these new astroviruses pose a risk of broader outbreaks or even cross-species transmission, as the Astrovirus family is known to infect many mammals and birds.
Understanding how a virus crosses the body’s natural barriers is crucial for preventing severe disease. Finn’s findings show that the newly discovered MLB and VA astrovirus strains may use their spike proteins to weaken the barriers that protect vital organs. This allows them to spread farther through the bloodstream than classical strains and potentially cause neurological and respiratory illnesses. His research may be especially important for protecting people with weakened immune systems, who are more vulnerable to severe complications from infections.
“It definitely made me more of a germaphobe,” Finn admitted. “But it also made me appreciate how much these small discoveries contribute to bigger goals like vaccines and disease prevention. These small steps add up.” As emerging viruses continue to evolve and expand their reach, research like this highlights the importance of studying viral proteins, not just entire viruses, to anticipate and control new infectious threats.
