Lyssavirus infection: 'low dose, multiple exposure' in the mouse model

Area of Science:

• Veterinary Virology
• Zoonotic Disease Research
• Pathogen Transmission Studies

Background:

• European bat lyssaviruses (EBLV-1, EBLV-2) are zoonotic viruses found in European bats.
• Lyssavirus maintenance and transmission within bat colonies are not well understood.
• The role of seropositive bats in disease dynamics remains unclear.

Purpose of the Study:

• To investigate the effects of repeated low-dose lyssavirus inoculation in a murine model.
• To mimic hypothesized natural infection routes for EBLV and rabies virus (RABV).
• To analyze clinical and serological responses following multiple exposures.

Main Methods:

• Mice were inoculated peripherally with standardized doses of EBLV-1, EBLV-2, or RABV.
• Four inoculations were administered over four months, with doses in alternating footpads.
• Antibody responses were monitored via blood sampling between inoculations.

Main Results:

• Clinical disease occurred after initial and subsequent inoculations, with varying percentages across virus types.
• The lowest doses induced disease in some mice upon first exposure.
• While some mice showed disease after secondary exposure, primary inoculation was the likely cause of death; tertiary and quaternary inoculations did not predictably alter outcomes or serological responses.

Conclusions:

• Repeated exposure to lyssaviruses does not reliably predict clinical disease or serological response in this model.
• Mechanisms underlying survival after multiple lyssavirus exposures require further investigation.
• The study highlights the complexity of lyssavirus dynamics and host response.