title: Postexposure treatment with the live-attenuated rabies virus (RV) vaccine TriGAS triggers the clearance of wild-type RV from the Central Nervous System (CNS) through the rapid induction of genes relevant to adaptive immunity in CNS tissues.
abstract: Postexposure treatment (PET) of wild-type rabies virus (RV)-infected mice with a live-attenuated triple-glycoprotein RV variant (TriGAS) promotes survival but does not prevent the pathogenic RV from invading and replicating in the brain. Successful PET is associated with the induction of a robust virus-neutralizing antibody response and clearance of the wild-type RV from brain tissues. Comparison of the transcriptomes of normal mouse brain with those of wild-type-RV-infected mice that had received either mock or TriGAS PET treatment revealed that many of the host genes activated in the mock-treated mice represent type I interferon (IFN) response genes. This indicates that RV infection induces an early type I IFN response that is unable to control the infection. In contrast, most of the activated genes in the brain of the RV-infected, TriGAS-treated mouse play a role in adaptive immunity, including the regulation of T cell activation, T cell differentiation, and the regulation of lymphocyte and mononuclear cell proliferation. These findings were confirmed by quantitative PCR (qPCR) array studies, which showed that 3 genes in particular, encoding chemokine ligand 3 (Ccl3), natural killer cell activator 2 (interleukin 12B [IL-12B]), and granzyme A (GzmA), were activated earlier and to a greater extent in the brains of RV-infected mice treated with TriGAS than in the brains of mock-treated mice. The activation of these genes, known to play key roles in the regulation of lymphocyte and mononuclear cell proliferation, is likely an important part of the mechanism by which TriGAS mediates its PET activity.
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Li
authors.forename: Adam
authors.initials: A
authors.lastname: Ertel
authors.forename: Carla
authors.initials: C
authors.lastname: Portocarrero
authors.forename: Darryll A
authors.initials: DA
authors.lastname: Barkhouse
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dietzschold
authors.forename: D Craig
authors.initials: DC
authors.lastname: Hooper
authors.forename: Milosz
authors.initials: M
authors.lastname: Faber
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology* / Q000821:virology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D056990:Post-Exposure Prophylaxis; D011818:Rabies / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000276:immunology* / Q000627:therapeutic use; D011820:Rabies virus / Q000276:immunology*; D015854:Up-Regulation; D014613:Vaccines, Attenuated / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000914:Antibodies, Viral; D011819:Rabies Vaccines; D014613:Vaccines, Attenuated