[4] The virus was first proven to infect humans in June 2009 when two farmers, living 60 miles (97 km) apart, presented with fever, fatigue, diarrhea, thrombocytopenia, and leukopenia.

[6] In 2013, researchers from the CDC and Missouri Western State University first isolated the Heartland virus (HRTV) from the Lone Star Tick (Amblyomma americanum).

In a 2015 retrospective study using convenience samples of different wild animal sera deer, raccoon, coyotes, and moose had antibodies against HRTV.

They lived in thirteen states: Florida, Georgia, Illinois, Indiana, Kansas, Kentucky, Missouri, North Carolina, Tennessee, Texas, but also New Hampshire, Maine and Vermont.

[8] Signs and symptoms include fever in excess of 100.4 °F (38 °C), lethargy (weakness), headaches, muscle pain (myalgia), loss of appetite, nausea, diarrhea, weight loss, joint pain (arthralgia), low white blood cell count (leukopenia) and easy bruising due to a low platelet count (thrombocytopenia).

[citation needed] Diagnosis is through the elimination of other causes of infectious diseases with related symptoms like ehrlichiosis and anaplasmosis or if the patient fails to respond to treatment with the antibiotic doxycycline.

[citation needed] More than 20 human infections have been reported in the United States,[12] but given the obscurity of the disease, the true number of cases is suspected to be substantially larger.