Intestinal infection and fecal shedding of infectious SFTS virus reveal a potential fecal–oral transmission route

Most people know that some diseases spread when a mosquito or tick bites, injecting a virus directly into the bloodstream. Others spread when we touch contaminated surfaces and then touch our mouths, a route known as fecal-oral transmission. For decades, scientists have understood that the severe fever with thrombocytopenia syndrome virus, or SFTSV, belongs to the first group. It is carried by ticks and passed to humans through their bites. This virus causes a dangerous illness marked by high fever and a dangerous drop in blood platelets, often leading to death in nearly eight out of every hundred patients. While doctors have long noticed that many infected people suffer from stomach problems like vomiting and diarrhea, the prevailing view was that these symptoms were just a side effect of the body fighting a massive infection elsewhere. The gut was thought to be a passive victim of the chaos, not an active site where the virus was multiplying.

A team of researchers from medical centers in China has now challenged this long-held assumption. By combining data from hundreds of sick patients with experiments in mice and human tissue grown in a lab, they found that the virus does not just pass through the gut; it actively invades and destroys the lining of the intestines. More importantly, they discovered that the virus replicates inside the intestine and is released into the stool as a fully infectious agent. This finding suggests that the disease might spread from person to person through contaminated feces, a route that has been overlooked until now. If this new transmission path is confirmed, it could change how hospitals protect staff and how communities manage outbreaks, moving beyond the simple rule of avoiding tick bites.

The investigation began with a look back at the records of 752 patients hospitalized with confirmed SFTSV infections across several hospitals. The researchers found that nearly two-thirds of these patients had experienced gastrointestinal symptoms, with diarrhea being the most common. They noticed a clear pattern: the higher the amount of virus in a patient's blood, the more likely they were to have severe stomach issues. To see if the gut was truly inflamed, they tested stool samples from a subset of patients. The vast majority showed high levels of a protein called calprotectin, a reliable sign that the intestinal lining is irritated and inflamed. This was not just a vague feeling of sickness; the data pointed to a specific, active problem within the digestive tract.

To understand exactly what was happening inside the gut, the scientists turned to mice that had been engineered to lack a specific immune defense, making them highly susceptible to the virus. When these mice were infected, they quickly developed severe diarrhea. Upon examining their intestines, the researchers saw that the virus had targeted the tiny, finger-like projections that line the gut, which are responsible for absorbing nutrients. The virus did not just float by; it infected the cells that make up the gut wall and the stem cells that are supposed to repair and renew that wall. This dual attack caused the gut lining to break down, leading to leakage and the watery stool observed in the animals. The virus seemed to prefer the small intestine, where it found the specific receptors it needed to enter the cells, leaving the large intestine relatively untouched.

The team then wanted to know if this same process happened in humans, not just in mice. They grew tiny, three-dimensional models of human intestines in a lab dish. These models, known as organoids, are made of real human intestinal cells that behave much like the tissue inside a person. When they exposed these organoids to the virus, the human cells became infected and started producing new virus particles. The virus triggered the same inflammatory response and weakened the barriers that keep the gut contents separate from the rest of the body. Crucially, this happened even without the presence of immune cells, proving that the gut lining itself is a direct target for the virus, not just a bystander caught in a systemic storm.

The most significant discovery came when the researchers asked a simple but difficult question: Is the virus in the stool alive and capable of causing infection, or is it just dead genetic material? They took stool samples from the infected mice and from twelve human patients in the acute phase of their illness. They processed these samples and introduced them to healthy cells in a lab. In both the mouse and human samples, the virus grew and multiplied, proving that infectious, replication-competent virus was being shed in the feces. In the human cases, the ability to isolate the live virus was linked to higher levels of virus in the blood, suggesting that this shedding happens when the infection is at its peak.

These findings reshape the understanding of how SFTSV spreads. While the tick remains the primary way the virus enters the human population, the study provides strong evidence that once a person is infected, they can potentially pass the virus to others through fecal contamination. This could explain why some clusters of infection occur in households or hospitals without any obvious tick exposure. The virus appears to turn the intestine into a factory, damaging the gut lining and releasing new virus particles into the environment. This new perspective suggests that infection control measures need to be broader, accounting for the possibility of fecal-oral transmission alongside the known risks of tick bites. The research does not claim that this is the main way the virus spreads, but it establishes a clear, previously unrecognized pathway that demands attention from public health officials and clinicians.