Down-regulation of HIV-1 infection by inhibition of the MAPK signaling pathway

Gong, Jianping; Shen, Xihui; Chen, C.; Qiu, Hui; Yang, Rongge

doi:10.1007/s12250-011-3184-y

Cited by 27 publications

(19 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggested that MAPKs inhibitors, ERK, p38 and JNK, were involved in the microfilaments of IPEC-J2 cells. In addition, inhibition of MAPKs also decreased the PEDV and TGEV infection, which was consistent with the report that the effect of MAPK pathway inhibitors on HIV infection (Gong et al, 2011). However, the relationship between the PEDV and TGEV infection and MAPK pathway remains to be further investigated.…”

Section: Discussionsupporting

confidence: 90%

Transmissible gastroenteritis virus and porcine epidemic diarrhoea virus infection induces dramatic changes in the tight junctions and microfilaments of polarized IPEC-J2 cells

et al. 2014

View full text Add to dashboard Cite

Viral infection converts the normal constitution of a cell to optimise viral entry, replication, and virion production. These conversions contain alterations or disruptions of the tight and adherens junctions between cells as part of their pathogenesis, and reorganise cellular microfilaments that initiate, sustain and spread the viral infections and so on. Using porcine epidemic diarrhoea virus (PEDV), transmissible gastroenteritis virus (TGEV) and a model of normal intestinal epithelial cells (IPEC-J2), we researched the interaction between tight and adherens junctions and microfilaments of IPEC-J2 cells with these viruses. In our work, the results showed that IPEC-J2 cells were susceptible to TGEV and PEDV infection. And TGEV could impair the barrier integrity of IPEC-J2 cells at early stages of infection through down-regulating some proteins of tight and adherens junctions, while PEDV cloud cause a slight of damage in the integrity of epithelial barrier. In addition, they also could affect the microfilaments remodelling of IPEC-J2 cells, and the drug-interfered microfilaments could inhibit viral replication and release. Furthermore, PEDV+TGEV co-infection was more aggravating to damage of tight junctions and remodelling of microfilaments than their single infection. Finally, the PEDV and TGEV infection affected the MAPK pathway, and inhibition of MAPK pathway regulated the changes of tight junctions and microfilaments of cells. These studies provide a new insight from the perspective of the epithelial barrier and microfilaments into the pathogenesis of PEDV and TGEV.

show abstract

Section: Discussionsupporting

confidence: 90%

Transmissible gastroenteritis virus and porcine epidemic diarrhoea virus infection induces dramatic changes in the tight junctions and microfilaments of polarized IPEC-J2 cells

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Of these, the most extensive studies are ERK1/2, JNKs and p38 MAPKs. As previously reported, JNK1/2 and/or p38 MAPK pathways is required for infection and replication of human immunodeficiency virus type 1, encephalomyocarditis virus, coxsackievirus B3, hepatitis C virus, herpes simplex virus 1, and the severe acute respiratory syndrome coronavirus [13][14][15][16][17][18]. The diverse effects of JNK1/2 and p38 MAPK activation by these viruses include induction of apoptosis in infected cells and enhancement of viral replication.…”

mentioning

confidence: 65%

Activation of JNK1/2 and p38 MAPK signaling pathways promotes enterovirus 71 infection in immature dendritic cells

Peng¹,

Shi²,

Zhang³

et al. 2014

BMC Microbiol

View full text Add to dashboard Cite

Backgroundc-Jun NH2-terminal kinase/stress-activated kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38 MAPK) are important components of cellular signal transduction pathways, which have been reported to be involved in viral replication. However, little is known about JNK1/2 and p38 MAPK signaling pathways in enterovirus 71 (EV71)-infected immature dendritic cells (iDCs). Thus, iDCs were induced from peripheral blood mononuclear cells (PBMC) and performed to explore the expressions and phosphorylation of molecules in the two signaling pathways as well as secretions of inflammatory cytokines and interferons during EV71 replication.ResultsWe showed that EV71 infection could activate both JNK1/2 and p38 MAPK in iDCs and phosphorylate their downstream transcription factors c-Fos and c-Jun, which further promoted the production of IL-2, IL-6, IL-10, and TNF-α. Moreover, EV71 infection also increased the release of IFN-β and IL-12 p40. Pretreatment of iDCs with SP600125 and SB203580 (20 μM) could severely impair viral replication and its induced phosphorylation of JNK1/2,p38 MAPK, c-Fos and c-Jun. In addition, treatment of EV71-infected iDCs with SP600125 and SB203580 could inhibit secretions of IL-6, IL-10 and TNF-α.ConclusionJNK1/2 and p38 MAPK signaling pathways are beneficial to EV71 infection and positively regulate secretions of inflammatory cytokines in iDCs.

show abstract

“…Potential anti-inflammatory compounds are also known to target different signaling pathways to attenuate the inflammatory response. In particular, MAPKs are widely known to be involved in various pathological processes associated with HIV-1 infection (such as neurotoxicity, macrophage activation, viral replication) [49]. Studies have further demonstrated that inhibition of these kinases can downregulate HIV-1 infection as well as decrease transcellular transport of HIV-1 across blood-brain barrier in vitro [49-51].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, MAPKs are widely known to be involved in various pathological processes associated with HIV-1 infection (such as neurotoxicity, macrophage activation, viral replication) [49]. Studies have further demonstrated that inhibition of these kinases can downregulate HIV-1 infection as well as decrease transcellular transport of HIV-1 across blood-brain barrier in vitro [49-51]. Therefore, we examined these pathways in our gp120-associated brain inflammation model and observed activation of ERK1/2 and JNKs in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Role of anti-inflammatory compounds in human immunodeficiency virus-1 glycoprotein120-mediated brain inflammation

Ashraf

Jiang

Hoque

et al. 2014

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundNeuroinflammation is a common immune response associated with brain human immunodeficiency virus-1 (HIV-1) infection. Identifying therapeutic compounds that exhibit better brain permeability and can target signaling pathways involved in inflammation may benefit treatment of HIV-associated neurological complications. The objective of this study was to implement an in vivo model of brain inflammation by intracerebroventricular administration of the HIV-1 viral coat protein gp120 in rats and to examine anti-inflammatory properties of HIV adjuvant therapies such as minocycline, chloroquine and simvastatin.MethodsMale Wistar rats were administered a single dose of gp120ADA (500 ng) daily for seven consecutive days, intracerebroventricularly, with or without prior intraperitoneal administration of minocycline, chloroquine or simvastatin. Maraviroc, a CCR5 antagonist, was administered intracerebroventricularly prior to gp120 administration for seven days as control. Real-time qPCR was used to assess gene expression of inflammatory markers in the frontal cortex, hippocampus and striatum. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) secretion in cerebrospinal fluid (CSF) was measured applying ELISA. Protein expression of mitogen-activated protein kinases (MAPKs) (extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinases (JNKs) and P38 kinases (P38Ks)) was detected using immunoblot analysis. Student’s t-test and ANOVA were applied to determine statistical significance.ResultsIn gp120ADA-injected rats, mRNA transcripts of interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) were significantly elevated in the frontal cortex, striatum and hippocampus compared to saline or heat-inactivated gp120-injected controls. In CSF, a significant increase in TNF-α and IL-1β was detected. Maraviroc reduced upregulation of these markers suggesting that the interaction of R5-tropic gp120 to CCR5 chemokine receptor is critical for induction of an inflammatory response. Minocycline, chloroquine or simvastatin attenuated upregulation of IL-1β and iNOS transcripts in different brain regions. In CSF, minocycline suppressed TNF-α and IL-1β secretion, whereas chloroquine attenuated IL-1β secretion. In gp120-injected animals, activation of ERK1/2 and JNKs was observed in the hippocampus and ERK1/2 activation was significantly reduced by the anti-inflammatory agents.ConclusionsOur data demonstrate that anti-inflammatory compounds can completely or partially reverse gp120-associated brain inflammation through an interaction with MAPK signaling pathways and suggest their potential role in contributing towards the prevention and treatment of HIV-associated neurological complications.

show abstract

Down-regulation of HIV-1 infection by inhibition of the MAPK signaling pathway

Cited by 27 publications

References 28 publications

Transmissible gastroenteritis virus and porcine epidemic diarrhoea virus infection induces dramatic changes in the tight junctions and microfilaments of polarized IPEC-J2 cells

Transmissible gastroenteritis virus and porcine epidemic diarrhoea virus infection induces dramatic changes in the tight junctions and microfilaments of polarized IPEC-J2 cells

Activation of JNK1/2 and p38 MAPK signaling pathways promotes enterovirus 71 infection in immature dendritic cells

Role of anti-inflammatory compounds in human immunodeficiency virus-1 glycoprotein120-mediated brain inflammation

Contact Info

Product

Resources

About