title: Minocycline differentially modulates viral infection and persistence in an experimental model of Japanese encephalitis.
abstract: Japanese encephalitis (JE) is caused by a neurotropic flavivirus that causes CNS damage that leads to death in acute cases or permanent neuropsychiatric sequel in survivors. The course of infection of this virus is not well defined though it is clear that it evades the host's innate immune response in the periphery. The current study was designed to investigate the time-dependent changes in the spleen and lymph node, apart from the CNS that are infected by the Japanese encephalitis virus (JEV). Our previous studies have led to the identification of minocycline, a semi-synthetic antibiotic, as a protective drug in JE. In this study we have also investigated the role of minocycline on the peripheral organs that are infected by JEV. Levels of IL-12 and MCP-1 in the organs were estimated by cytometric bead array, and immunohistochemical studies were performed on cryosections of tissue to detect CD3- or CD11b-positive cells as well as JEV antigen. We found that the levels of T cell-activating cytokine IL-12 and MCP-1 levels were significantly elevated in JEV-infected tissue samples in a time-dependent manner. Corresponding to this increase was the increase in the number of CD3- and CD11b-positive cells in the tissues of infected animals. Minocycline treatment abrogated these changes. Minocycline treatment also resulted in the gradual decrease in the number of CD11b (but not CD3) positive cells in the lymph node and spleen, even though the virus persisted in these organs. We also observed structural changes in the spleen following minocycline treatment.
authors.affiliation: National Brain Research Centre, Manesar, Haryana, India. kallol4u@gmail.com
authors.forename: Kallol
authors.initials: K
authors.lastname: Dutta
authors.forename: Kanhaiya Lal
authors.initials: KL
authors.lastname: Kumawat
authors.forename: Arshed
authors.initials: A
authors.lastname: Nazmi
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Mishra
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004195:Disease Models, Animal; D004672:Encephalitis, Japanese / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008911:Minocycline / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018664:Interleukin-12; D008911:Minocycline