Signaling Pathways Involved In Dengue-2 Virus Infection Induced RANTES Overexpression

Lee, Ying‐Ray; Lei, Huan Yao; Chen, Shun Hua; Wang, Jen Ren; Lin, Yee Shin; Yeh, Trai Ming; Liu, Ching Chuan; Liu, Hsiao Sheng

doi:10.3844/ajidsp.2008.32.40

Cited by 5 publications

(7 citation statements)

References 39 publications

(35 reference statements)

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“…Inhibition of phosphorylated ERK1/2 by FR180204 treatment decreases liver injury and improves clinical parameters in DENV-infected Balb/c mice ERK1/2 signaling has been implicated in the apoptosis and liver injury that occurs in rabbits infected with the rabbit hemorrhagic disease virus (Garcia-Lastra et al, 2009). Following DENV infection, phosphorylated p38 MAPK is induced in vitro (Ceballos-Olvera et al, 2010;Huerta-Zepeda et al, 2008;Lee et al, 2008;Nagila et al, 2013). Inhibition of phosphorylated p38 MAPK also reduces TNF-␣ production and apoptosis in DENV-infected HepG2 cells (Nagila et al, 2013).…”

Section: Apoptotic Gene Expression Profile In Liver Of Denv-infected mentioning

confidence: 87%

“…Statistical analysis was done by an unpaired t-test using GraphPad Prism 5 program and the data were represented as mean ± SEM. and ERK1/2 in Chang liver cells (Lee et al, 2008). However, the in vivo role of ERK1/2 has not been investigated.…”

Section: Apoptotic Gene Expression Profile In Liver Of Denv-infected mentioning

confidence: 98%

“…Following DENV infection, phosphorylated p38 MAPK is induced (Ceballos-Olvera et al, 2009;Huerta-Zepeda et al, 2008;Lee et al, 2008;Nagila et al, 2013). Inhibition of p38 MAPK reduces DENV-mediated apoptosis of HepG2 cell line (Nagila et al, 2013).…”

Section: Introductionmentioning

confidence: 96%

“…However, the role of ERK1/2 during DENV infection remains unclear. Activation of ERK1/2 occurs during DENV infection of liver cells, human endothelial cells and macrophages (Ceballos-Olvera et al, 2010;Huerta-Zepeda et al, 2008;Lee et al, 2008), but is blocked in the DENV-infected human alveolar epithelial carcinoma cell line (Chang et al, 2012). To evaluate the role of ERK1/2 in the pathogenesis of DENV infection, we examined the influence of ERK1/2 activation on DENV-mediated apoptosis in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Role of ERK1/2 signaling in dengue virus-induced liver injury

et al. 2014

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Section: Apoptotic Gene Expression Profile In Liver Of Denv-infected mentioning

confidence: 87%

Section: Apoptotic Gene Expression Profile In Liver Of Denv-infected mentioning

confidence: 98%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Role of ERK1/2 signaling in dengue virus-induced liver injury

et al. 2014

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“…HCV infection activates the Ras/Raf/MEK pathway, resulting in the attenuation of the interferon-JAK-STAT pathway and stimulation of HCV replication (51). Dengue virus serotype 2 (DENV-2) participates in liver inflammation by inducing the expression of various chemokines through activating all three MAPK pathways (52). YFV infection induces ERK1/2 activation, and treatment with U0126 reduces the level of YFV replication by 99% (38).…”

Section: Discussionmentioning

confidence: 99%

Suppression of Zika Virus Infection and Replication in Endothelial Cells and Astrocytes by PKA Inhibitor PKI 14-22

Cheng

Silva

Huang

et al. 2018

J Virol

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The recent outbreak of Zika virus (ZIKV), a reemerging flavivirus, and its associated neurological disorders, such as Guillain-Barré (GB) syndrome and microcephaly, have generated an urgent need to develop effective ZIKV vaccines and therapeutic agents. Here, we used human endothelial cells and astrocytes, both of which represent key cell types for ZIKV infection, to identify potential inhibitors of ZIKV replication. Because several pathways, including the AMP-activated protein kinase (AMPK), protein kinase A (PKA), and mitogen-activated protein kinase (MAPK) signaling pathways, have been reported to play important roles in flavivirus replication, we tested inhibitors and agonists of these pathways for their effects on ZIKV replication. We identified the PKA inhibitor PKI 14-22 (PKI) to be a potent inhibitor of ZIKV replication. PKI effectively suppressed the replication of ZIKV from both the African and Asian/American lineages with a high efficiency and minimal cytotoxicity. While ZIKV infection does not induce PKA activation, endogenous PKA activity is essential for supporting ZIKV replication. Interestingly, in addition to PKA, PKI also inhibited another unknown target(s) to block ZIKV replication. PKI inhibited ZIKV replication at the postentry stage by preferentially affecting negative-sense RNA synthesis as well as viral protein translation. Together, these results have identified a potential inhibitor of ZIKV replication which could be further explored for future therapeutic application.IMPORTANCE There is an urgent need to develop effective vaccines and therapeutic agents against Zika virus (ZIKV) infection, a reemerging flavivirus associated with neurological disorders, including Guillain-Barré (GB) syndrome and microcephaly. By screening for inhibitors of several cellular pathways, we have identified the PKA inhibitor PKI 14-22 (PKI) to be a potent inhibitor of ZIKV replication. We show that PKI effectively suppresses the replication of all ZIKV strains tested with minimal cytotoxicity to human endothelial cells and astrocytes, two key cell types for ZIKV infection. Furthermore, we show that PKI inhibits ZIKV negative-sense RNA synthesis and viral protein translation. This study has identified a potent inhibitor of ZIKV infection which could be further explored for future therapeutic application.

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Expression of nitric oxide synthase and nitric oxide levels in peripheral blood cells and oxidized low-density lipoprotein levels in saliva as early markers of severe dengue

Hapugaswatte

Perera

Premaratna

et al. 2019

Preprint

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41Objectives: To identify suitable biomarkers during early stages of dengue to predict which 42 patients would develop severe forms of dengue before the warning signs appear. 43Methods: Expression of inducible nitric oxide synthase (iNOS) and resultant changes in nitric 44 oxide (NO) and oxidized low density lipoprotein (oxLDL) levels in plasma and saliva were 45 analyzed. 46Results: Expression of iNOS in patients who later developed dengue hoemorrhagic fever (DHF) 47 showed significant (P<0.05) down regulation compared to dengue fever (DF) patients while 48 those who later developed DHF showed a corresponding significant (P<0.05) decrease of plasma 49 NO levels (18.1±3.1 µM) compared to DF patients (23.6±4.4 µM) within 4 days from fever 50 onset. OxLDL levels in plasma showed a decrease in patients who later developed DHF 51 compared to DF patients although this value was significantly different only within 3 days from 52 fever onset. The salivary NO levels did not show a significant difference. However, salivary 53 oxLDL levels were significantly (P<0.05) low in patients who later developed DHF (0.6±0.2 54 ng/mL) compared to DF patients (1±0.4 ng/mL) collected within 4 days from fever onset. 55Conclusions: The expression level of iNOS, plasma NO and salivary oxLDL levels may serve as 56 early markers of severity of dengue infection. 57 58 Keywords: Dengue, Dengue Hemorrhagic Fever, inducible nitric oxide synthase, nitric oxide, 59 oxidized LDL, salivary biomarkers 60 61 Highlights 62  Severity of dengue infection correlates with early differential expression of iNOS 63  Plasma NO and salivary oxLDL levels may also serve as early markers of severe dengue 64  Saliva may serve as a non-invasive source of early biological markers for severity of 65 dengue infection 66 67 68 Dengue is an extremely prevalent mosquito-borne viral disease in many tropical countries 69 including Sri Lanka. It is the second most important tropical disease (after malaria) with 284 -70 528 million dengue infections resulting in 67 -136 million clinically manifested dengue cases 71 with half the global population at-risk posing a significant public health threat worldwide. 1,2 In 72 2017, 1,86,101 suspected dengue cases were reported to the Epidemiology Unit of Sri Lanka 73 from all over the island. 3 Most people infected with dengue viruses are asymptomatic while 74 others may suffer a wide range of clinical manifestations from mild fever to severe dengue. 75 Although a serious, debilitating condition, dengue fever (DF) is not fatal while severe 76 manifestations of the disease such as dengue hoemorrhagic fever (DHF) and dengue shock 77 syndrome (DSS) are major causes of hospitalization and death, globally. 1,4 Currently, the number 78 of DHF cases in Sri Lanka has dramatically increased. 5 Unlike DF, severe dengue is 79 characterized by severe possibly lethal vasculopathy marked with plasma leakage, intrinsic 80 coagulopathy and massive internal bleeding. 6,7 81 Despite the social and clinical impact, there are no antiviral thera...

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Signaling Pathways Involved In Dengue-2 Virus Infection Induced RANTES Overexpression

Cited by 5 publications

References 39 publications

Role of ERK1/2 signaling in dengue virus-induced liver injury

Role of ERK1/2 signaling in dengue virus-induced liver injury

Suppression of Zika Virus Infection and Replication in Endothelial Cells and Astrocytes by PKA Inhibitor PKI 14-22

Expression of nitric oxide synthase and nitric oxide levels in peripheral blood cells and oxidized low-density lipoprotein levels in saliva as early markers of severe dengue

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