Charting the Secret Frontier of the Human Astrovirus

The precise location in human receptor cells, where the astrovirus capsid spike entry takes place was unveiled by researchers from the lab of Rebecca DuBois at the University of California, Santa Cruz. Human astrovirus frequently attacks kids and older people contributing to stomach flu. Conditions such as fever, diarrhea, and vomiting are caused by the stomach flu. Especially young children from low-income nations, often face life-threatening cycles of malnutrition due to astrovirus infection. (1^✔ ✔Trusted Source
Structure of the human astrovirus capsid spike in complex with the neonatal Fc receptor

Go to source)

The astrovirus is commonly detected in wastewater, circulating largely in public communities. At present, no vaccine exists for this dangerous virus.

However, the revelation of the secret spot of viral entry in human cells opens the clear route for designing new drugs and potential vaccines to defend against human astrovirus and to safeguard young children and older adults. The study was published in Nature Communications.

The New Era of Astrovirus Combat

“We uncovered a really important part of the virus lifecycle, and now we know exactly where on the virus this important interaction with the human receptor occurs,” DuBois said. “Now we can develop vaccines that will target it and block that interaction—it really guides future vaccine development.”

The team’s discovery also illuminates the possibility of repurposing existing, FDA-approved treatments to target astrovirus. DuBois and her team will continue to pursue both vaccines and treatments for astrovirus, with the support of around $416,000 via a new R21 award from National Institutes of Health.

The DuBois lab at the Baskin School of Engineering studies the molecular structure of viruses—mostly those that primarily affect children—to understand how they enter human cells and reveal new targets for vaccines and treatments.

Why Molecular Mapping Matters for Understanding the Infection

Within the last two years, scientists discovered that astrovirus enters the body by binding to a protein in human cells called the neonatal Fc receptor. This receptor plays a key role in supplying antibodies to babies via breastmilk, and continues to support overall health later in life by moving antibodies and other proteins through the bloodstream.

However, it’s not enough to know what the virus binds to—it’s crucial to discover exactly how the binding works to allow the virus to enter the body. DuBois’ lab sought to understand how the virus engages this receptor at the molecular level.

“Viruses have to use host machinery to replicate, and the very first step is that the virus has to enter our cells,” said Adam Lentz, a Ph.D. student in DuBois’ lab who spearheaded this study. “That step of cell entry is where we're really interested, and we want to fully understand how this happens—what proteins, what receptors, what other human factors it's using to get inside.”

“Ultimately, once we understand how it enters our cells, we can take the next step of figuring out how to stop it.”

Vaccines, Drugs, and Repurposing Existing Treatments

To do so, the engineers created replicas of both the astrovirus and the receptor in the lab, mixing them together to observe exactly how and where the two bind. Using X-ray crystallography, a technique that reveals the structure of a protein at the atomic level, they discovered that the virus attaches to the same exact site on the receptor that antibodies do.

“The virus is hijacking the pathway that humans use for beneficial purposes to get inside the cell,” DuBois said. “I think that’s one of the most exciting findings—we discovered exactly how the virus is using this receptor to sneak into our cells.”

FDA-approved treatments already exist to target this antibody pathway for other disease contexts, such as for some types of auto-immunity. The research from the DuBois lab reveals a path to repurpose these treatments and test for their ability to protect against astrovirus disease —shortening the timeline for development of new therapies.

DuBois is particularly interested in developing vaccines for astrovirus, and the close study of astrovirus revealed that the pathogen frequently mutates near the location where it binds to the receptor. This means that the virus evolves often to evade the human immune system—much like influenza—and suggests that a multi-strain approach may be needed for an effective vaccine.

“If we can make a vaccine that is multivalent, we can protect against many strains of the virus,” DuBois said.

Reference:

1. Structure of the human astrovirus capsid spike in complex with the neonatal Fc receptor - (https://www.nature.com/articles/s41467-025-65203-2)

Source-Eurekalert