Abstract
Rabies is an important neglected disease, characterized by invariably fatal encephalitis. Several studies focus on understanding the pathogenic mechanisms of the prototype lyssavirus rabies virus (RABV) infection, and little is known about the pathogenesis of rabies caused by other lyssaviruses. We sought to characterize the host response to Duvenhage virus infection and compare it with responses observed during RABV infection by gene expression profiling of brains of mice with the respective infections. We found in both infections differentially expressed genes leading to increased expression of type I interferons (IFNs), chemokines, and proinflammatory cytokines. In addition several genes of the IFN signaling pathway are up-regulated, indicating a strong antiviral response and activation of the negative feedback mechanism to limit type I IFN responses. Furthermore we provide evidence that in the absence of significant neuronal apoptotic death, cell death of neurons is mediated via the pyroptotic pathway in both infections. Taken together, we have identified several genes and/or pathways for both infections that could be used to explore novel approaches for intervention strategies against rabies.
Highlights
Rabies is an important neglected disease, caused by any of the viruses belonging to the Lyssavirus genus of the family Rhabdoviridae
The pathogenic mechanisms that eventually lead to lethal rabies encephalitis are poorly understood
Most of the studies to elucidate rabies pathogenesis have been largely focused on classical rabies virus (RABV) infection, whereas pathogenic mechanisms of rabies encephalitis caused by other lyssavirus infections and especially by Duvenhage virus (DUVV) have received little attention
Summary
Rabies is an important neglected disease, caused by any of the viruses belonging to the Lyssavirus genus of the family Rhabdoviridae. The other members of the genus are geographically restricted and include: Lagos bat virus (LBV), Mokola virus (MOKV), Duvenhage virus (DUVV), Ikoma virus (IKOV), and Shimoni bat virus (SHIBV) all restricted to Africa; European bat lyssaviruses 1 and 2 (EBLV 1 and 2) and Bokeloh bat lyssavirus (BBLV), restricted to Europe; Australian bat lyssavirus (ABLV), restricted to Australia; Transcriptomics of Duvenahge Virus Infections. MOKV and IKOV are the only lyssaviruses that have not been associated with bats to date. All mammals can be infected with RABV, only a few species act as reservoir species and most commonly transmit the virus. RABV is transmitted by carnivores mainly dogs, foxes, and raccoons. Bats are the main carriers while a spillover infection to other mammals seem to be sporadic
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