Contact-Dependent Transmission of Langat and Tick-Borne Encephalitis Virus in Type I Interferon Receptor 1-Deficient Mice

Abstract

Tick-borne encephalitis is a severe disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). Every year, between 10,000 and 12,000 people become infected with this flavivirus. ABSTRACT Tick-borne encephalitis virus (TBEV) is transmitted to humans primarily through tick bites or oral consumption of accordingly contaminated unpasteurized milk or milk products. The detection of TBEV RNA in various body fluids in immunosuppressed human patients is documented. However, the risk of direct contact exposure remains unclear. Interferon alpha receptor 1-deficient (Ifnar1−/−) mice, which lack the interferon alpha/beta responses, develop neurologic manifestations after infection with TBEV and Langat virus (LGTV). We showed that subcutaneous, intranasal, and peroral infections of LGTV lead to disease, whereas mice with intragastric application of LGTV showed no disease signs. With LGTV infection, mice exhibit seroconversion, and significant viral RNA levels were detected in saliva, eye smear, feces, and urine. As a result, TBEV and LGTV are transmitted between mice from infected to naive cocaged sentinel animals. Although intranasal inoculation of LGTV is entirely sufficient to establish the disease in mice, the virus is not transmitted by aerosols. These pooled results from animal models highlight the risks of exposure to TBEV contaminants and the possibility for close contact transmission of TBEV in interferon alpha receptor 1-deficient laboratory mice. IMPORTANCE Tick-borne encephalitis is a severe disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). Every year, between 10,000 and 12,000 people become infected with this flavivirus. TBEV is usually transmitted to humans via the bite of a tick, but infections due to consumption of infectious milk products are being increasingly reported. Since there is no therapy for TBEV infection and the mechanisms of virus persistence in reservoir animals are unclear, it is important to highlight the risk of exposure to TBEV contaminants and know the possible routes of transmission of this virus. The significance of our research is in identifying other infection routes of TBEV and LGTV and the possibility of close contact transmission.