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MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11.

Ashraf U, Zhu B, Ye J, Wan S, Nie Y, Chen Z, Cui M, Wang C, Duan X, Zhang H, Chen H, Cao S - J. Virol. (2016)

Bottom Line: Japanese encephalitis virus (JEV) can invade the central nervous system and consequently induce neuroinflammation, which is characterized by profound neuronal cell damage accompanied by astrogliosis and microgliosis.The pathological features of JEV-induced encephalitis are inflammatory reactions and neurological diseases resulting from glia activation.The present study reveals that miR-19b-3p targets ring finger protein 11 in glia and promotes inflammatory cytokine production by enhancing nuclear factor kappa B activity in these cells.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China.

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Antagomir-19b-3p treatment stimulates RNF11 expression and reduces inflammatory cytokine production in a mouse model of JEV infection. Mice were treated with antagomir negative control or antagomir-19b-3p (60 mg/kg body weight) after JEV infection, and brain samples were collected at day 6 postinfection. PBS, samples collected from PBS-challenged mice; JEV-NC, samples collected from JEV-infected mice treated with antagomir negative control; JEV-antagomir, samples collected from JEV-infected mice treated with antagomir-19b-3p. (A) The increase of miR-19b-3p expression was abrogated in JEV-infected mice by administration of antagomir-19b-3p. (B and C) Suppression of RNF11 was reversed by antagomir-19b-3p treatment in JEV-infected mice. RNF11 mRNA (B) and protein (C) levels were determined by quantitative real-time PCR and immunoblotting, respectively. Protein levels were quantified by immunoblot scanning and normalized to the amount of GAPDH expression. (D) Antagomir-19b-3p treatment decreased the production of inflammatory cytokines. The protein levels of TNF-α, IL-6, and IL-1β were analyzed by ELISA. CCL5 mRNA levels were determined by quantitative real-time PCR and normalized to the expression of β-actin. The effects of antagomir-19b-3p and the antagomir negative control were compared using two-tailed Student's t tests. Similar results were obtained in three mice. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
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Figure 9: Antagomir-19b-3p treatment stimulates RNF11 expression and reduces inflammatory cytokine production in a mouse model of JEV infection. Mice were treated with antagomir negative control or antagomir-19b-3p (60 mg/kg body weight) after JEV infection, and brain samples were collected at day 6 postinfection. PBS, samples collected from PBS-challenged mice; JEV-NC, samples collected from JEV-infected mice treated with antagomir negative control; JEV-antagomir, samples collected from JEV-infected mice treated with antagomir-19b-3p. (A) The increase of miR-19b-3p expression was abrogated in JEV-infected mice by administration of antagomir-19b-3p. (B and C) Suppression of RNF11 was reversed by antagomir-19b-3p treatment in JEV-infected mice. RNF11 mRNA (B) and protein (C) levels were determined by quantitative real-time PCR and immunoblotting, respectively. Protein levels were quantified by immunoblot scanning and normalized to the amount of GAPDH expression. (D) Antagomir-19b-3p treatment decreased the production of inflammatory cytokines. The protein levels of TNF-α, IL-6, and IL-1β were analyzed by ELISA. CCL5 mRNA levels were determined by quantitative real-time PCR and normalized to the expression of β-actin. The effects of antagomir-19b-3p and the antagomir negative control were compared using two-tailed Student's t tests. Similar results were obtained in three mice. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Mentions: Similar to our in vitro findings, brain tissues from JEV-infected mice demonstrated an inverse relationship between the expression patterns of miR-19b-3p and its target, RNF11; i.e., higher miR-19b-3p expression was correlated with a reduced level of RNF11 (Fig. 9A to C). In JEV-infected mice, treatment of antagomir-19b-3p caused a specific reduction in miR-19b-3p expression and rescued the alterations in RNF11 levels (Fig. 9A to C). Moreover, we observed that inflammatory cytokines, including TNF-α, IL-6, IL-1β, and CCL5, were significantly augmented in JEV-infected mice treated with the antagomir negative control, whereas these cytokine levels were attenuated upon antagomir-19b-3p treatment (Fig. 9D). Because inflammatory cytokines are responsible for neuropathological and cytotoxic conditions during JEV infection (8, 26), a diminished level of cytokines upon antagomir-19b-3p treatment could be favorable in reducing neuronal cell damage.


MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11.

Ashraf U, Zhu B, Ye J, Wan S, Nie Y, Chen Z, Cui M, Wang C, Duan X, Zhang H, Chen H, Cao S - J. Virol. (2016)

Antagomir-19b-3p treatment stimulates RNF11 expression and reduces inflammatory cytokine production in a mouse model of JEV infection. Mice were treated with antagomir negative control or antagomir-19b-3p (60 mg/kg body weight) after JEV infection, and brain samples were collected at day 6 postinfection. PBS, samples collected from PBS-challenged mice; JEV-NC, samples collected from JEV-infected mice treated with antagomir negative control; JEV-antagomir, samples collected from JEV-infected mice treated with antagomir-19b-3p. (A) The increase of miR-19b-3p expression was abrogated in JEV-infected mice by administration of antagomir-19b-3p. (B and C) Suppression of RNF11 was reversed by antagomir-19b-3p treatment in JEV-infected mice. RNF11 mRNA (B) and protein (C) levels were determined by quantitative real-time PCR and immunoblotting, respectively. Protein levels were quantified by immunoblot scanning and normalized to the amount of GAPDH expression. (D) Antagomir-19b-3p treatment decreased the production of inflammatory cytokines. The protein levels of TNF-α, IL-6, and IL-1β were analyzed by ELISA. CCL5 mRNA levels were determined by quantitative real-time PCR and normalized to the expression of β-actin. The effects of antagomir-19b-3p and the antagomir negative control were compared using two-tailed Student's t tests. Similar results were obtained in three mice. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
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Figure 9: Antagomir-19b-3p treatment stimulates RNF11 expression and reduces inflammatory cytokine production in a mouse model of JEV infection. Mice were treated with antagomir negative control or antagomir-19b-3p (60 mg/kg body weight) after JEV infection, and brain samples were collected at day 6 postinfection. PBS, samples collected from PBS-challenged mice; JEV-NC, samples collected from JEV-infected mice treated with antagomir negative control; JEV-antagomir, samples collected from JEV-infected mice treated with antagomir-19b-3p. (A) The increase of miR-19b-3p expression was abrogated in JEV-infected mice by administration of antagomir-19b-3p. (B and C) Suppression of RNF11 was reversed by antagomir-19b-3p treatment in JEV-infected mice. RNF11 mRNA (B) and protein (C) levels were determined by quantitative real-time PCR and immunoblotting, respectively. Protein levels were quantified by immunoblot scanning and normalized to the amount of GAPDH expression. (D) Antagomir-19b-3p treatment decreased the production of inflammatory cytokines. The protein levels of TNF-α, IL-6, and IL-1β were analyzed by ELISA. CCL5 mRNA levels were determined by quantitative real-time PCR and normalized to the expression of β-actin. The effects of antagomir-19b-3p and the antagomir negative control were compared using two-tailed Student's t tests. Similar results were obtained in three mice. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Mentions: Similar to our in vitro findings, brain tissues from JEV-infected mice demonstrated an inverse relationship between the expression patterns of miR-19b-3p and its target, RNF11; i.e., higher miR-19b-3p expression was correlated with a reduced level of RNF11 (Fig. 9A to C). In JEV-infected mice, treatment of antagomir-19b-3p caused a specific reduction in miR-19b-3p expression and rescued the alterations in RNF11 levels (Fig. 9A to C). Moreover, we observed that inflammatory cytokines, including TNF-α, IL-6, IL-1β, and CCL5, were significantly augmented in JEV-infected mice treated with the antagomir negative control, whereas these cytokine levels were attenuated upon antagomir-19b-3p treatment (Fig. 9D). Because inflammatory cytokines are responsible for neuropathological and cytotoxic conditions during JEV infection (8, 26), a diminished level of cytokines upon antagomir-19b-3p treatment could be favorable in reducing neuronal cell damage.

Bottom Line: Japanese encephalitis virus (JEV) can invade the central nervous system and consequently induce neuroinflammation, which is characterized by profound neuronal cell damage accompanied by astrogliosis and microgliosis.The pathological features of JEV-induced encephalitis are inflammatory reactions and neurological diseases resulting from glia activation.The present study reveals that miR-19b-3p targets ring finger protein 11 in glia and promotes inflammatory cytokine production by enhancing nuclear factor kappa B activity in these cells.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei, People's Republic of China.

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Related in: MedlinePlus