Innate immune responses in raccoons after raccoon rabies virus infection

Abstract

Zoonotic wildlife diseases pose significant health risks not only to their primary vectors but also to humans and domestic animals. Rabies is a lethal encephalitis caused by rabies virus (RV). This RNA virus can infect a range of terrestrial mammals but each viral variant persists in a particular reservoir host. Active management of these host vectors is needed to minimize the negative impacts of this disease, and an understanding of the immune response to RV infection aids strategies for host vaccination. Current knowledge of immune responses to RV infection comes primarily from rodent models in which an innate immune response triggers activation of several genes and signalling pathways. It is unclear, however, how well rodent models represent the immune response of natural hosts. This study investigates the innate immune response of a primary host, the raccoon, to a peripheral challenge using the raccoon rabies virus (RRV). The extent and temporal course of this response during RRV infection was analysed using genes predicted to be upregulated during infection (IFNs; IFN regulatory factors; IL-6; Toll like receptor-3; TNF receptor). We found that RRV activated components of the innate immune system, with changes in levels of transcripts correlated with presence of viral RNA. Our results suggest that natural reservoirs of rabies may not mimic the immune response triggered in rodent models, highlighting the need for further studies of infection in primary hosts.

Molecular Mechanisms of Raccoon Rabies Virus Progression in Its Natural Host

“…Examination of viral expression both temporally and spatially, enhances our understanding of the behaviour of the virus after peripheral infection; it also provides insight into the replication strategies that the virus employs to establish a successful infection such as restriction of the glycoprotein expression. Similar to Srithayakumar et al [14], this study shows that the initiation of the immune response after the virus enters the CNS is not sufficient to control it, as the replication of the virus increases significantly upon entry into the CNS. The majority of studies to date examine only nucleoprotein and glycoprotein to elucidate pathogenic determinants of the virus, whereas we examined the entire genome of the RRV to better understand the role of viral genetics on the virulence.…”

“…This suggests that the virus may have been attenuated in this particular sample, hence the increased replication and transcription that was observed. It is interesting to note that genes associated with the interferon pathway, as well as inflammatory cytokines, and viral receptors were also expressed in this particular sample [14]. When comparing results of this study, to Srithayakumar et al [14], it is evident that the presence of the virus was vital for the initiation of the immune response.…”

“…It is interesting to note that genes associated with the interferon pathway, as well as inflammatory cytokines, and viral receptors were also expressed in this particular sample [14]. When comparing results of this study, to Srithayakumar et al [14], it is evident that the presence of the virus was vital for the initiation of the immune response. In this study, we found viral genes to be expressed at low levels at the site of inoculation in two of the samples (Figure 1(a)), however in the same samples the earliest time point to detect the genes indicative of the innate immune response was in the spinal cord and brain.…”

“…In this study, we found viral genes to be expressed at low levels at the site of inoculation in two of the samples (Figure 1(a)), however in the same samples the earliest time point to detect the genes indicative of the innate immune response was in the spinal cord and brain. From the expression patterns noted in this study, and the immune response data obtained from Srithayakumar et al [14], there is a weak correlation between the expression of glycoprotein and the initiation of the immune response.…”

“…Uncontrolled replication of virus in the central nervous system (CNS) leads to disease and ultimately death. Despite the high lethality of RV, variation has been noted in the host's immune response and histopathological changes caused by the virus [10]- [14]; suggesting that factors governing the regulation of virulence of RV are diverse. Although rabies has been extensively studied over the past century, pathogenic mechanisms by which rabies infection results in neurological disease and causes death in natural reservoirs are not clear [15] [16] [18].…”