title: Suppressed expression of miR-378 targeting gzmb in NK cells is required to control dengue virus infection.
abstract: Dengue virus (DENV) remains a major public health threat because no vaccine or drugs are available for the prevention and treatment of DENV infection, and the immunopathogenesis mechanisms of DENV infection are not fully understood. Cytotoxic molecules, such as granzyme B (GrzB), may be necessary to control viral infections. However, the exact role of GrzB during DENV infection and the mechanisms regulating GrzB expression during DENV infection are not clear. This study found that miR-27a*, miR-30e, and miR-378 were down-regulated in DENV-infected patients, and DENV infection in humans induced a significant up-regulation of GrzB in natural killer (NK) cells and CD8(+) T cells. Further investigation indicated that NK cells, but not CD8(+) T cells, were the major sources of GrzB, and miR-378, but not miR-27a* or miR-30e, suppressed GrzB expression in NK cells. Notably, we found that overexpression of miR-378 using a miR-378 agomir in DENV-infected mice inhibited GrzB expression and promoted DENV replication. These results suggest the critical importance of miR-378 in the regulation of GrzB expression and a protective role for GrzB in controlling DENV replication in vivo. Therefore, this study provides a new insight into the immunopathogenesis mechanism of DENV infection and a biological basis for the development of new therapeutic strategies to control DENV infection.
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Lingming
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Si
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Junmei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Danyun
authors.initials: D
authors.lastname: Fang
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Gucheng
authors.initials: G
authors.lastname: Zeng
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000070416:Antagomirs / Q000494:pharmacology; D001483:Base Sequence; D003715:Dengue / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D003716:Dengue Virus / Q000187:drug effects / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D054353:Perforin / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000070416:Antagomirs; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D054353:Perforin; D053804:Granzymes