Abstract
The rabies virus (RABV) is highly neurotropic and it uses evasive strategies to successfully evade the host immune system. Because rabies is often fatal, understanding the basic processes of the virus-host interactions, particularly in the initial events of infection, is critical for the design of new therapeutic approaches to target RABV. Here, we examined the possible role of dendritic cells (DCs) in the transmission of RABV to neural cells at peripheral site of exposure. Viral replication only occurred at a low level in the DC cell line, JAWS II, after its infection with either pathogenic RABV (CVS strain) or low-pathogenic RABV (ERA strain), and no progeny viruses were produced in the culture supernatants. However, both viral genomic RNAs were retained in the long term after infection and maintained their infectivity. The biggest difference between CVS and ERA was in their ability to induce type I interferons. Although the ERA-infected JAWS II cells exhibited cytopathic effect and were apparently killed by normal spleen cells in vitro, the CVS-infected JAWS II cells showed milder cytopathic effect and less lysis when cocultured with spleen cells. Strongly increased expression of major histocompatibility complex classes I, costimulatory molecules (CD80 and CD86), type I interferons and Toll- like receptor 3, and was observed only in the ERA-inoculated JAWS II cells and not in those inoculated with CVS. During the silencing of the cellular immune response in the DCs, the pathogenic CVS strain cryptically maintained an infectious viral genome and was capable of transmitting infectious RABV to permissive neural cells. These findings demonstrate that DCs may play a role in the passive carriage of RABV during natural rabies infections.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-419) contains supplementary material, which is available to authorized users.
Highlights
Innate immunity is the first line of defense against invading pathogens and encompasses several reactions that target the initial phases of viral infections
Infectious Rabies virus (RABV) at an MOI of 10 or 30 gradually decreased under cell-free conditions (CVS or ERA + medium, in Figure 1A) as a natural result because the virus could not survive without infection into the cells, a more rapid decline in infectivity was observed in the presence of JAWS II cells (CVS or ERA + JAWS II, in Figure 1A), indicating that RABV was promptly ingested by the cells and that no infectious virus remained in the culture medium
To examine the potential role of Dendritic cells (DC) in the transmission of RABV, we focused on the probable events that occur at the site of injury caused by rabid animals, by looking into the migration of RABV toward the central nervous system (CNS), which is the organ most permissive to RABV
Summary
Innate immunity is the first line of defense against invading pathogens and encompasses several reactions that target the initial phases of viral infections. Rabies virus (RABV) is a highly neurotropic negative-stranded RNA virus that spreads along the neural pathway and invades the central nervous system (CNS), where it causes an acute and often fatal infection (Finke and Conzelmann 2005). One of the characteristic features of RABV is its ability to reach the CNS in spite of inducing an immune response that can eliminate the virus (Feder et al 2012). This ability is considered important during the initial stages of peripheral infection following an animal bite, the most common route of transmission, as the virus moves from the muscle or subcutaneous tissue to the peripheral neuronal cells. Reaching the CNS represents a critical stage in the establishment of the infection, the pathogenesis and detailed mechanism of host evasion and the preservation of RABV during these early stages are not well understood
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