Contact-dependent transmission of Langat and tick-borne encephalitis virus in type I interferon receptor-1 deficient mice

Sarah Schreier; Kristin Cebulski; Andrea Kröger

doi:10.1128/JVI.02039-20

Contact-dependent transmission of Langat and tick-borne encephalitis virus in type I interferon receptor-1 deficient mice

J Virol. 2021 Mar 25;95(8):e02039-20. doi: 10.1128/JVI.02039-20. Epub 2021 Jan 27.

Authors

Sarah Schreier¹, Kristin Cebulski¹, Andrea Kröger^{2

3}

Affiliations

¹ Molecular Microbiology Group, Institute of Medical Microbiology, Otto von Guericke University Magdeburg, Magdeburg, Germany.
² Molecular Microbiology Group, Institute of Medical Microbiology, Otto von Guericke University Magdeburg, Magdeburg, Germany andrea.kroeger@med.ovgu.de.
³ Innate Immunity and Infection Group, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.

Abstract

Tick-borne encephalitis virus (TBEV) is primarily transmitted to humans 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 are lacking the interferon-α/β responses, develop neurologic manifestations after infection with TBEV and Langat virus (LGTV). We showed that subcutaneous, intranasal, and peroral infection of LGTV lead to disease, whereas mice with intragastric application of LGTV showed no disease signs. With LGTV infected mice exhibit seroconversion and significant viral RNA levels was detected in saliva, eye smear, feces and urine. As a result, TBEV and LGTV are transmitted between mice from infected to naïve co-caged 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 10,000-12,000 people become infected with this flavivirus. The TBEV is usually transmitted to humans via the bite of a tick, but infections due to consumption of infectious milk products are increasingly being reported. Since there is no therapy for an TBEV infection and mechanisms of virus persistence in reservoir animals are unclear, it is important to highlight the risk of exposure to TBEV contaminants and know 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.