What was the first human disease proven to be caused by a virus?

Yellow fever was the first human disease proven to be caused by a virus.

At the end of the nineteenth century, scientists suspected that yellow fever was infectious, but they did not yet understand agents smaller than bacteria. In 1900–1901, the U.S. Army Yellow Fever Commission, including Walter Reed, showed that the disease could be transmitted by mosquitoes and that the infectious agent passed through filters that trapped bacteria. These findings provided the first convincing proof that a human disease was caused by a virus.

The yellow fever virus is an enveloped RNA virus in the genus Flavivirus. It is maintained in mosquito–primate transmission cycles in tropical regions of Africa and South America. In humans, infection may cause fever, headache, muscle pain, nausea, and jaundice; severe cases can produce bleeding, liver failure, and death.

Yellow fever is often confused with diseases such as malaria because both are mosquito-borne and can cause fever. They are caused by entirely different kinds of pathogens. A highly effective vaccine, based on the 17D strain developed in the 1930s, remains central to prevention, while mosquito control reduces transmission.