The Role of Pattern Recognition Receptors in Japanese Encephalitis Virus Infection

Japanese encephalitis virus (JEV), a member of the Flaviviridae family, can cause severe encephalitis and is responsible up to 15,000 deaths per year. Despite the clinical significance of this virus, there is relatively little information on the role of innate immune mechanisms involved in the response to infection. In the current issue of Viral Immunology, Fadnis and colleagues have investigated the involvement of Pattern Recognition Receptors (PRRs) in JEV infection in a mouse neuronal cell line (Neuro 2a) as compared to JEV infected suckling and adult mice. Their data indicate that TLR (Toll-Like Receptor) 3 gene exhibited differential expression in JEV-infected Neuro2a, suckling mice and adult mouse brain cells, as compared to controls. Gene silencing of TLR3 resulted in a significant enhancement of JEV replication, supporting the hypothesis that the TLR3 serves a protective role against JEV infection. The authors additionally show that other PRRs, such as TLR2, also appear to be involved in controlling JEV infection. These data further advance our understanding of the innate response to this important virus.

Other articles in this issue of Viral Immunology touch on a range of topics. Rudraraju et al. have investigated the distribution of T cells in the respiratory tract tissues of mice that were infected with Sendai virus (SeV). Confocal imaging of T cells that had been transferred into animals infected with SeV showed that the cells maximized distances between each donor cell and its nearest neighbor. Upregulation of RANTES, CXCL9, CXCL10, and CCL2 in the cells has led the authors to speculate that the cells use chemokines and cytokines to mark their territories to avoid cell overlap and to enhance virus clearance. In the area of vaccine development, Quan et al. have compared several known adjuvants, Alum, CpG DNA, monophosphoryl lipid A (MPL), poly IC, Gardiquimod, and cholera toxin (CT), for their ability to promote immune responses to influenza virus-like particles (VLPs). Their data suggest that Alum, MPL, or CpG adjuvants are the most effective mucosal adjuvants for influenza VLP-based vaccines. The adjuvanting effects of interleukin 4 (IL-4) have been studies by Peng and colleagues. These authors investigated the capacity of swine interleukin-4 to enhance virus-specific immune responses elicited by a live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. Interestingly, swine IL-4 markedly enhanced the protective immune response of pigs and improved the efficacy of the vaccine at preventing disease. Finally, Post et al. have evaluated the contribution of the NS1 gene of H7 avian influenza virus strains to pathogenicity in chickens. The NS1 genes of two closely related viruses differentially affected weight loss, viral load in the brain, type I interferon, and pro-inflammatory cytokines in the brains, and mortality. However, there were minimal differences in type I interferon expression in the lungs of chickens implicating a critical role for pro-inflammatory cytokines in vital organs such as the brain.

Taken together, the articles presented in the current issue of Vial Immunology advance our understanding of several aspects of the immune response to viral infection ranging from innate to adaptive immunity, from mucosal to systemic immunity, and from mice to economically important veterinary species. The findings outlined here will be important for future vaccine development.