A 16-year-old boy from north central Florida has made history in the least glamorous way – he has become the first documented case of a human Keystone virus infection.
The virus – first isolated from a mosquito in Keystone, Florida, in 1964 – belongs to the same North American genus as the La Crosse, Jamestown Canyon, and California encephalitis viruses; strains that may cause potentially fatal brain inflammation.
Yet, as described in the journal Clinical Infectious Diseases, the patient presented with just a transient low-grade fever, sore throat, and – most notably – a rash of non-itchy, painless, red bumps that formed first on his chest then spread to his abdomen, arm, back, and face. He reported having been bit by multiple mosquitos during the last several evenings, while he was attending summer band camp. Two days after visiting the clinic, and without any medical treatment, his rash disappeared.

Given that past research has established that the Keystone virus is commonly carried by mosquitos in coastal regions stretching from the Chesapeake Bay, through Florida, and as far west as Texas, the team of physicians, epidemiologists, and geneticists who diagnosed the teen believe that humans have likely been infected many times in the past.
This hypothesis is bolstered by the fact that studies conducted in the 1960’s found that about 19 to 21 percent of people living in those areas display seropositivity for the Keystone virus – meaning that their immune system generated antibodies against the virus after an episode of exposure.
“However, actual isolation of KEYV from humans has never been reported, nor has it been linked with a clinical syndrome in humans, despite its apparent endemicity in animals and mosquitoes,” the authors note, explaining that squirrels, rabbits, and whitetail deer are other known reservoirs.
“While we cannot say definitely that the virus was responsible for the rash and reported fever, our data are clearly suggestive, and raise the possibility that a proportion of what are otherwise unremarkable ‘rash and fever’ cases seen in primary care settings in coastal areas of the southeastern United States actually reflect KEYV infections.”
To observe viral transfection and replication, the team took Keystone virus particles isolated from the patient’s urine and added them to laboratory cultures of kidney-derived epithelial and neural precursor cells. Despite the lack of evidence that Keystone causes more severe viral symptoms (such as high fever, muscle aches, and gastrointestinal distress), the readiness with which this strain infected the neural cells led the authors to worry that it could possibly cause encephalitis as well.
Moving forward, they recommend that Keystone should be considered in instances of viral encephalitis that evade other diagnoses.