Up-regulation of chemokine gene transcripts and T-cell infiltration into the central nervous system and dorsal root ganglia are characteristics of experimental European bat lyssavirus type 2 infection of mice

Abstract

European bat lyssaviruses (EBLV) types 1 and 2 are closely related to classical rabies virus (RABV), and are capable of causing rabies in terrestrial mammals, including humans. The authors have investigated the murine host innate immune response in the brain, salivary gland, spinal cord, and blood, following peripheral inoculation with EBLV-2. In the brain, increases in Toll-like receptor-3 (TLR-3) transcript preceded overt disease, with a range of inflammatory gene transcripts increasing during the clinical stage of infection. This included transcripts for interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and CXC chemokine ligand 10 (CXCL10). In the salivary gland, there was a small but significant increase of CXCL10 gene transcript and a limited increase in 2'-5' oligoadenylate synthetase (2'-5' OAS1) transcript. In the blood, there was an increase in levels of IFN-gamma and virus-neutralizing antibodies (VNAs) were detected prior to the appearance of clinical signs. These changes were associated with severe lymphocyte infiltration observed within the spinal cord and dorsal root ganglia (DRG), which was dominated by T lymphocytes and associated with widespread inflammatory changes. The authors speculate that the increase of inflammatory cytokines and chemokines in response to EBLV-2 infection leads to a dramatic increase in T-cell infiltration and provides evidence for a robust immune response to lyssavirus infection that may not commonly occur in RABV infection.