The high level of virus present in the synganglion has been proposed to help the virus persist through the metamorphosis of the tick, as the nervous system undergoes less remodeling than other systems. Vertebrates In the laboratory setting, several members of the genus cause severe disease in mice and hamsters. Systemic spread of the virus occurs, with pathological effects present in multiple organs and systems, including the brain, liver, lymphatic system, and sometimes the lungs and small intestine. Lymphocytes are a major target cell for DHOV. DHOV infection in mice resembles experimental influenza infection in mice and ferrets as well as fatal H5N1 influenza infection of humans, and has been proposed as a model for this disease. Natural infections with thogotoviruses in mammals generally do not appear to result in symptoms. THOV is a significant veterinary pathogen, for example, causing a febrile illness and abortion in sheep. As of February 2015, only eight cases of human disease associated with thogotoviruses have been reported: two with THOV, five with DHOV and one with Bourbon virus; there have been two fatalities. The incubation period for THOV is 4–5 days. All three viruses were associated with fever. THOV and DHOV also caused neurological symptoms: meningitis and neuromyelitis optica in the case of THOV; encephalitis in the case of DHOV. Hepatitis has been observed with THOV. The single case of disease in a person infected with Bourbon virus was associated with decreases in blood platelets and white cells; no neurological symptoms were observed. Influenza-like respiratory symptoms have not been reported. Treatment and prevention No specific treatment or vaccine is available for thogotoviruses, as of February 2015. The antiviral drug ribavirin, which has a broad spectrum of activity that includes some other orthomyxoviruses, has been shown to inhibit DHOV replication in vitro in a single study. Supportive therapy is used for THOV disease, and has been recommended by the US Centers for Disease Control and Prevention for infection with Bourbon virus. As with other arboviruses, avoidance of contact with the vector is central to prevention. Species and strains Two species have been confirmed by the ICTV, THOV and DHOV. The two viruses have a low degree of sequence identity (37% for the nucleoprotein; 31% for the envelope glycoprotein), and their antibodies do not crossreact. Batken virus is a subtype of DHOV. As of February 2015, a further five species or strains have been suggested as