Keystone virus (genus Orthobunyavirus, family Peribunyaviridae) is a negative-sense single-stranded RNA virus that predominantly infects mammals, including rabbits, raccoons, squirrels, and white-tailed deer. It is transmitted by mosquitoes, particularly Aedes atlanticus. The virus was first isolated from mosquitoes in Keystone, Florida, where its name derives. It has subsequently been identified in animals and mosquitoes throughout the coastal southeastern United States, from the Chesapeake Bay to Texas.

Although studies conducted in the 1960s demonstrated that 19%-21% of humans living in the Tampa Bay area were seropositive for the virus, there has only been one confirmed case of clinical disease associated with Keystone virus infection. The patient was a 16-year-old man who presented in 2016 with a low-grade fever and diffuse nonpruritic skin rash. The rash started on his chest, progressively spread, and resolved within two days. It was exacerbated by heat and sunlight. He had no other symptoms. Although the authors of the case report admitted that they could not definitively prove causality, the data was suggestive. They concluded that many of the individuals that present with transient rash and fever in endemic regions could actually represent Keystone virus infections.