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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 reduces neuroinflammation and improves the survival rate in JEV-infected mice. (A) Antagomir-19b-3p treatment ameliorates histopathological changes in JEV-infected mice. H&E staining of brain sections was performed to examine the pathological changes. Scale bar, 100 μm. (B and C) Antagomir-19b-3p treatment reduces astrocytosis and microgliosis. Sections of brain were analyzed by IHC staining. (B) Activation of astrocytes was detected by anti-GFAP antibody (B). Activation of microglia was detected by anti-IBA-1 antibody (C). Scale bar, 50 μm. (D) Antagomir-19b-3p treatment decreases neuronal cell damage. The apoptotic cells in the brain sections were stained using a TUNEL assay kit. Scale bar, 100 μm. The figures are a representative of three mice with similar results. (E) Antagomir-19b-3p treatment improves the survival rate. Survival of mice in each group was recorded for 25 days after JEV infection (100 PFU/mice) intracranially. Data were collected and are shown as Kaplan-Meier survival curves (n = 5 for each group). (F) Behavior score chart showing the gradual alleviation of suffering following JEV infection. Behavior scoring is as follows: 0, no restriction of movement, no frequent blinking, no body stiffening, no hind limb paralysis; 1, no restriction of movement, frequent blinking, no body stiffening, no hind limb paralysis; 2, restriction of movement, frequent blinking, no body stiffening, no hind limb paralysis; 3, restriction of movement, body stiffening, no hind limb paralysis; 4, restriction of movement, closed eyes, body stiffening, hind limb paralysis, body tremors.
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Figure 10: Antagomir-19b-3p treatment reduces neuroinflammation and improves the survival rate in JEV-infected mice. (A) Antagomir-19b-3p treatment ameliorates histopathological changes in JEV-infected mice. H&E staining of brain sections was performed to examine the pathological changes. Scale bar, 100 μm. (B and C) Antagomir-19b-3p treatment reduces astrocytosis and microgliosis. Sections of brain were analyzed by IHC staining. (B) Activation of astrocytes was detected by anti-GFAP antibody (B). Activation of microglia was detected by anti-IBA-1 antibody (C). Scale bar, 50 μm. (D) Antagomir-19b-3p treatment decreases neuronal cell damage. The apoptotic cells in the brain sections were stained using a TUNEL assay kit. Scale bar, 100 μm. The figures are a representative of three mice with similar results. (E) Antagomir-19b-3p treatment improves the survival rate. Survival of mice in each group was recorded for 25 days after JEV infection (100 PFU/mice) intracranially. Data were collected and are shown as Kaplan-Meier survival curves (n = 5 for each group). (F) Behavior score chart showing the gradual alleviation of suffering following JEV infection. Behavior scoring is as follows: 0, no restriction of movement, no frequent blinking, no body stiffening, no hind limb paralysis; 1, no restriction of movement, frequent blinking, no body stiffening, no hind limb paralysis; 2, restriction of movement, frequent blinking, no body stiffening, no hind limb paralysis; 3, restriction of movement, body stiffening, no hind limb paralysis; 4, restriction of movement, closed eyes, body stiffening, hind limb paralysis, body tremors.

Mentions: On day 6 postinfection, brain sections from PBS- or JEV-challenged mice were examined for pathological variations. Brains of antagomir negative-control-treated mice presented the emblematic histopathological features of encephalitis, whereas pathological changes were ameliorated upon antagomir-19b-3p treatment (Fig. 10A). JEV infection is also associated with marked activation of astrocytes and microglia (26, 36). An aberrant increase in the number of astrocytes and microglia was detected by IHC using anti-GFAP and -IBA-1 antibody, respectively. Reactive astrocytosis and microgliosis were noticed in the antagomir negative-control-treated group, while antagomir-19b-3p treatment reduced the proliferation of these glial cells markedly (Fig. 10B and C). To examine whether antagomir-19b-3p can reduce neuronal cell damage, brain sections were subjected to a TUNEL assay. The number of dead cells was significantly lower with antagomir-19b-3p treatment in JEV-infected mice than in antagomir negative-control-treated mice (Fig. 10D). These findings indicate that antagomir-19b-3p treatment has the potential to abrogate the activation of astrocytes and microglia and to subsequently reduce neuronal cell death.


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 reduces neuroinflammation and improves the survival rate in JEV-infected mice. (A) Antagomir-19b-3p treatment ameliorates histopathological changes in JEV-infected mice. H&E staining of brain sections was performed to examine the pathological changes. Scale bar, 100 μm. (B and C) Antagomir-19b-3p treatment reduces astrocytosis and microgliosis. Sections of brain were analyzed by IHC staining. (B) Activation of astrocytes was detected by anti-GFAP antibody (B). Activation of microglia was detected by anti-IBA-1 antibody (C). Scale bar, 50 μm. (D) Antagomir-19b-3p treatment decreases neuronal cell damage. The apoptotic cells in the brain sections were stained using a TUNEL assay kit. Scale bar, 100 μm. The figures are a representative of three mice with similar results. (E) Antagomir-19b-3p treatment improves the survival rate. Survival of mice in each group was recorded for 25 days after JEV infection (100 PFU/mice) intracranially. Data were collected and are shown as Kaplan-Meier survival curves (n = 5 for each group). (F) Behavior score chart showing the gradual alleviation of suffering following JEV infection. Behavior scoring is as follows: 0, no restriction of movement, no frequent blinking, no body stiffening, no hind limb paralysis; 1, no restriction of movement, frequent blinking, no body stiffening, no hind limb paralysis; 2, restriction of movement, frequent blinking, no body stiffening, no hind limb paralysis; 3, restriction of movement, body stiffening, no hind limb paralysis; 4, restriction of movement, closed eyes, body stiffening, hind limb paralysis, body tremors.
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Related In: Results  -  Collection

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Show All Figures
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Figure 10: Antagomir-19b-3p treatment reduces neuroinflammation and improves the survival rate in JEV-infected mice. (A) Antagomir-19b-3p treatment ameliorates histopathological changes in JEV-infected mice. H&E staining of brain sections was performed to examine the pathological changes. Scale bar, 100 μm. (B and C) Antagomir-19b-3p treatment reduces astrocytosis and microgliosis. Sections of brain were analyzed by IHC staining. (B) Activation of astrocytes was detected by anti-GFAP antibody (B). Activation of microglia was detected by anti-IBA-1 antibody (C). Scale bar, 50 μm. (D) Antagomir-19b-3p treatment decreases neuronal cell damage. The apoptotic cells in the brain sections were stained using a TUNEL assay kit. Scale bar, 100 μm. The figures are a representative of three mice with similar results. (E) Antagomir-19b-3p treatment improves the survival rate. Survival of mice in each group was recorded for 25 days after JEV infection (100 PFU/mice) intracranially. Data were collected and are shown as Kaplan-Meier survival curves (n = 5 for each group). (F) Behavior score chart showing the gradual alleviation of suffering following JEV infection. Behavior scoring is as follows: 0, no restriction of movement, no frequent blinking, no body stiffening, no hind limb paralysis; 1, no restriction of movement, frequent blinking, no body stiffening, no hind limb paralysis; 2, restriction of movement, frequent blinking, no body stiffening, no hind limb paralysis; 3, restriction of movement, body stiffening, no hind limb paralysis; 4, restriction of movement, closed eyes, body stiffening, hind limb paralysis, body tremors.
Mentions: On day 6 postinfection, brain sections from PBS- or JEV-challenged mice were examined for pathological variations. Brains of antagomir negative-control-treated mice presented the emblematic histopathological features of encephalitis, whereas pathological changes were ameliorated upon antagomir-19b-3p treatment (Fig. 10A). JEV infection is also associated with marked activation of astrocytes and microglia (26, 36). An aberrant increase in the number of astrocytes and microglia was detected by IHC using anti-GFAP and -IBA-1 antibody, respectively. Reactive astrocytosis and microgliosis were noticed in the antagomir negative-control-treated group, while antagomir-19b-3p treatment reduced the proliferation of these glial cells markedly (Fig. 10B and C). To examine whether antagomir-19b-3p can reduce neuronal cell damage, brain sections were subjected to a TUNEL assay. The number of dead cells was significantly lower with antagomir-19b-3p treatment in JEV-infected mice than in antagomir negative-control-treated mice (Fig. 10D). These findings indicate that antagomir-19b-3p treatment has the potential to abrogate the activation of astrocytes and microglia and to subsequently reduce neuronal cell death.

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