Vesicular stomatitis virus (VSV) is a livestock virus that causes painful blisters in the mouths and on the hooves of horses, cattle, and pigs. It belongs to the Vesiculovirus genus within the Rhabdoviridae family, the same viral family that includes rabies. While VSV rarely causes serious illness in humans, it has become one of the most important tools in modern virology, serving as the backbone for an Ebola vaccine and as an experimental cancer treatment.
What VSV Looks Like and How It Works
Under a microscope, VSV has a distinctive bullet shape, roughly 70 nanometers wide and 170 nanometers long. It carries a single strand of RNA wrapped in a protective envelope. That RNA encodes just five proteins, making it one of the simpler viruses scientists work with. One of those proteins, the glycoprotein (G), sits on the virus’s outer surface and acts like a key: it latches onto a host cell, gets pulled inside through a pocket in the cell membrane, and then uses the acidic environment inside the cell to crack open and release its genetic material. From there, the virus hijacks the cell’s machinery to make copies of itself.
This simplicity is part of what makes VSV so attractive to researchers. With only five genes, it’s relatively easy to modify in the lab, swapping out its surface protein for one from a different virus entirely.
Symptoms in Livestock
VSV primarily affects horses, cattle, and pigs. Clinical signs appear 2 to 8 days after exposure. The first thing ranchers typically notice is excessive drooling or frothing at the mouth. Inside the animal’s mouth, raised, whitish blisters form on the lips, gums, tongue, and dental pad. These blisters swell and eventually rupture, leaving raw, painful sores that make eating and drinking difficult. Affected animals often lose weight.
Blisters can also develop on the nose, ears, udders, and around the coronary band, which is the area where the hairline meets the hoof. When lesions form there, animals may become visibly lame. Fever often appears before or alongside the first blisters. Most animals recover on their own within two weeks, but the economic impact on farms can be significant due to lost productivity and mandatory quarantine.
How VSV Spreads
VSV is classified as an arbovirus, meaning it spreads primarily through biting insects. During U.S. outbreaks, two groups of insects play the biggest role: Culicoides biting midges and Simulium black flies. These insects introduce the virus into herds and continue spreading it between animals even when livestock aren’t being moved. Direct contact between animals and contaminated equipment can also transmit the virus, but insect vectors are the main drivers of outbreaks.
Outbreaks in the United States tend to occur in warmer months when insect populations peak, and they cluster in southwestern and western states. The virus circulates year-round in parts of Central and South America.
Reporting and Quarantine Rules
Vesicular stomatitis is a reportable disease in the United States, meaning any suspected case must be immediately reported to state or federal animal health authorities. This strict requirement exists because VSV blisters look nearly identical to those caused by foot-and-mouth disease, a far more devastating illness. Rapid laboratory testing is needed to tell them apart.
The USDA maintains eight approved laboratories that can confirm VSV through complement fixation testing and PCR. Once a case is confirmed, the affected farm is placed under quarantine until at least 14 days after the last animal develops lesions. If the virus keeps spreading within the premises, that quarantine period extends accordingly, sometimes lasting weeks.
Risk to Humans
VSV can infect people, but it’s uncommon and typically mild. Veterinarians, laboratory workers, and ranchers who handle infected animals are the most likely to be exposed. When human infection does occur, it generally produces flu-like symptoms: fever, muscle aches, headache, and fatigue. Serious complications are rare. The virus does not spread from person to person in any meaningful way.
VSV as an Ebola Vaccine
The most high-profile medical use of VSV is as the platform for the Ebola vaccine known as rVSV-ZEBOV. Scientists engineered this vaccine by removing VSV’s own surface glycoprotein and replacing it with the surface protein from Zaire Ebolavirus. The result is a virus that can still replicate and trigger a strong immune response, but the immune system learns to recognize Ebola rather than VSV.
The vaccine was put to the test during the 2014-2016 West African Ebola outbreak in a landmark trial in Guinea. Researchers used a “ring vaccination” strategy, vaccinating the close contacts of confirmed Ebola cases. Among people who received the vaccine immediately, zero cases of Ebola occurred from 10 days after vaccination onward, compared to 23 cases among those who were not vaccinated or received delayed vaccination. The estimated vaccine efficacy was 100%, with a 95% confidence interval of 79.3% to 100%. This trial provided the evidence that led to the vaccine’s approval and its continued use in Ebola outbreaks across Central and West Africa.
VSV in Cancer Treatment
Researchers are also exploring VSV as an oncolytic virus, one that selectively infects and destroys cancer cells while leaving healthy tissue largely intact. Healthy cells have robust antiviral defenses that can shut down VSV replication, but many cancer cells have lost those defenses, making them vulnerable.
A phase 1 clinical trial tested a modified version of VSV in patients with metastatic uveal melanoma, a rare and aggressive eye cancer with limited treatment options. The engineered virus was designed to produce human interferon-beta (which helps protect normal cells) along with a protein found on melanoma cells to stimulate an immune response against the tumor. The virus was administered both directly into tumors and intravenously. A separate phase 1 trial evaluated a related VSV construct in patients with relapsed blood cancers, confirming that intravenous delivery was safe.
These trials are still in early stages, focused on safety and immune response rather than proving the treatment cures cancer. But they represent a growing body of work using VSV’s simple, modifiable structure as a platform for targeting cancers that resist conventional therapy.