Exploring the role of infected keratinocytes during rabies virus infection.

Rabies virus (RABV), a lyssavirus causing fatal encephalitis, is primarily transmitted via dog bites, though superficial exposures such as scratches or bat bites can also result in infection. The mechanisms underlying transmission through these minor exposures remain unclear. This study investigated the involvement of epidermal keratinocytes in RABV entry. RABV antigen was detected in keratinocytes at inoculation sites in experimentally infected mice and at potential viral entry sites in naturally infected dogs. However, keratinocyte infection could not be replicated in ex vivo skin biopsies from mice or dogs, nor was antigen detected in pre-clinical skin samples. Furthermore, superficial exposure via the inner ear skin of mice did not result in infection. Thus, it remains unclear whether keratinocytes are initially infected or become infected later due to centrifugal spread of RABV. Nonetheless, our findings highlight the need to better understand keratinocyte involvement, especially in superficial RABV exposure.