Extraneural Rabies Virus Infection Leads To Tissue Damage And Cell Death In Mice

Rabies, a fatal neurological disease caused by Lyssavirus rabies (RABV), poses a significant threat to public health globally. Despite extensive studies on RABV-induced neuropathology, the involvement of extraneural organs during rabies pathogenesis and the tropisms of wild-type strains to different organs remain largely unknown. Here, we investigated the tropism of a dog and bat RABV variant to three different extraneural tissues (kidneys, lungs and liver) and characterized cellular and tissue damage associated with infection in mice over 30 days. Our results reveal that RABV may have a tropism for the kidneys and cause tissue-specific cellular damage. Furthermore, we propose that RABV spreads to extraneural tissues simultaneously with central nervous system (CNS) infection. Understanding the involvement of extraneural organs in rabies pathogenesis may contribute to the development of effective treatment strategies of this fatal disease. AUTHOR SUMMARYRabies is a lethal viral infection that targets the nervous system and generally can be transmitted to humans by bites of infected animals. While there has been significant research focused on how the virus damages the brain, little is known about how the infection affects other organs in the periphery. To address this knowledge gap, we conducted an experimental study to investigate the effects of two distinct wild strains of the virus, one isolated from dogs and the other from bats, on the lungs, liver, and kidneys in mice model of infection. Our findings suggest that the rabies virus infection leads to cell death and produces specific lesions in each of these organs, and we hypothesize that rabies virus may spread to these tissues at the same time as the brain, which possible contributes to the disease outcome. These findings enhance our understanding on how rabies virus targets organs outside the nervous system and its pathology in these different systems.