Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's Sarcoma-associated herpesvirus by herpes simplex virus type 1

Qin, Di; Feng, Na; Fan, Weifei; Ma, Xinting; Yan, Qin; Lv, Zhigang; Zeng, Yi; Zhu, Jianzhong; Liu, Chun

doi:10.1186/1471-2180-11-240

Cited by 51 publications

(43 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…JUN pathways play a critical role in malignant transformation. It could be activated in infected cells by herpesviruses such as EBV and KSHV [37,38,39]. The expression of JUN was also found to be upregulated in infected thymuses.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Analysis of Host Responses to Marek's Disease Virus Infection in Chicken Thymus

Qin²,

et al. 2015

Intervirology

View full text Add to dashboard Cite

Marek's disease virus (MDV) is a cell-associated alpha-herpesvirus that causes T-cell lymphomas and nervous disorders in chickens. Different from other lymphoid organs, the thymus is the site of T-cell maturation and differentiation. However, the transcriptional response to MDV infection in the chicken thymus is still not known. In this study, we performed genome-wide expression analysis in thymus tissues of RB1B-infected chickens at different time points to investigate the molecular mechanisms of MDV pathogenesis. The number of differentially expressed genes with 2-fold or higher changes (>2) are as follows: 1,250 genes (7 dpi), 834 genes (14 dpi), 1,958 genes (21 dpi), and 2,306 genes (28 dpi). Gene ontology enrichment analysis revealed that the upregulated genes were involved in immune and inflammatory response at 7 dpi; angiogenesis, cytoskeleton organization, cell adhesion, and signal transduction showed different expressions at 21 and 28 dpi. The expression pattern of 18 randomly selected genes was confirmed by real-time RT-PCR. Several differently expressed host genes associated with tumor development are discussed. We identified the global host-gene expression pattern in the thymus of chickens that responded to MDV infection. The present data may provide groundwork for future investigation in the biology and pathogenesis of MDV.

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptional Analysis of Host Responses to Marek's Disease Virus Infection in Chicken Thymus

Qin²,

et al. 2015

Intervirology

View full text Add to dashboard Cite

show abstract

“…The expression of GFP indicates the presence of KSHV genome, while that of RFP signifies the entry into viral lytic replication. BCBL-1 and BC-3 cells were electroporated as described previously (47)(48)(49)(50)(51). The efficiency of transfection in BCBL-1 or BC-3 was monitored by cotransfection with plasmid pEGFP-N2 (Clontech Laboratories, Palo Alto, CA), which contains the enhanced GFP gene fused to the cytomegalovirus immediate-early gene promoter.…”

Section: Methodsmentioning

confidence: 99%

“…The first part was treated with DNase and proteinase K (10 mg/ml) before viral DNA extraction (55). Real-time DNA-PCR was carried out on viral DNA extracted essentially as described previously (49). The KSHV ORF26 gene cloned in pcDNA3.1 (Invitrogen) was used to generate the standard curve.…”

Section: Western Blot Analysismentioning

confidence: 99%

Inhibition of Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication by HIV-1 Nef and Cellular MicroRNA hsa-miR-1258

Yan

Shen

et al. 2014

J Virol

Self Cite

View full text Add to dashboard Cite

Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several AIDS-related malignancies, including IMPORTANCEThis study found that Nef, a secreted HIV-1 protein, suppressed KSHV lytic replication to promote KSHV latency. Mechanistic studies indicated that a Nef-upregulated cellular miRNA, hsa-miR-1258, inhibits KSHV replication by directly targeting a seed sequence in the KSHV RTA 3=UTR. These results illustrate that, in addition to viral miRNAs, cellular miRNAs also play an important role in regulating the life cycle of KSHV. Overall, this is the first study to report the involvement of Nef in KSHV latency, implying its likely important role in the pathogenesis of AIDS-related malignancies.

show abstract

“…p35 levels are induced secondarily to neurotrophic factors that stimulate extracellular-signal-regulated kinase 1/2 (ERK1/2), activating the transcription factor Egr1 (36)(37)(38). Interestingly, a previous report showed that HSV-1 infection activates the ERK/mitogen-activated protein kinase (MAPK) signaling pathway (39). Moreover, it has been shown that HSV-1 lytic infection induces Egr1 in rabbit corneal cells (40).…”

mentioning

confidence: 99%

Herpes Simplex Virus 1 Upregulates p35, Alters CDK-5 Localization, and Stimulates CDK-5 Kinase Activity during Acute Infection in Neurons

Mostafa

Sels

Davido

2015

J Virol

View full text Add to dashboard Cite

The cyclin-dependent kinase 5 (CDK-5) activating protein, p35, is important for acute herpes simplex virus 1 (HSV-1) replication in mice. This report shows that HSV-1 increases p35 levels, changes the primary localization of CDK-5 from the nucleus to the cytoplasm, and enhances CDK-5 activity during lytic or acute infection. Infected neurons also stained positive for the DNA damage response (DDR) marker ␥H2AX. We propose that CDK-5 is activated by the DDR to protect infected neurons from apoptosis. Herpes simplex virus 1 (HSV-1) is a human pathogen that establishes lifelong latent infection in sensory neurons (1, 46). It is not well understood how the virus switches from lytic to latent infections in neurons and the mechanisms involved in reversing this switch under stress stimuli to initiate reactivation. It is vital that the neurons survive an infection by HSV-1 if the virus is to efficiently establish a latent infection or reactivate. Not surprisingly, HSV-1 has developed countermeasures to prevent neuronal apoptosis, in part, with the expression of the latency-associated transcripts (LATs) (2-4). While the contribution of viral gene products that possess antiapoptotic activities has been a major area of interest in HSV-1 research, the role of cellular factors involved in neuronal survival has received limited attention.One neuronal factor that is highly active in postmitotic neurons and is required for neuronal survival during stress is cyclindependent kinase 5 (CDK-5) (5, 6). CDK-5 regulates many neuronal processes (reviewed in reference 7) and has been shown to play important roles in both neuronal survival and death. Inactivation of CDK-5 has been shown to trigger neuronal death (8-11). On the other hand, a survival function for CDK-5 is evident when neurons are stressed (12-16). For its activation, CDK-5 binds to p35 or a related protein, p39, which also modulate CDK-5's subcellular localization (17)(18)(19)(20). Notably the activity of CDK-5 directly correlates with the levels of its major activator, p35, and both are expressed predominantly in neurons (21), which likely explains why CDK-5 is mainly active in neurons, although it is constitutively expressed in many cell types (17,22).We have previously shown that HSV-1 acute replication is impaired in the eyes and trigeminal ganglia (TG) of p35 knockout mice, reducing the establishment of latency and reactivation (23). Given this previous result, we sought to determine whether HSV-1 altered the expression or subcellular localization of the p35 and CDK-5 proteins during acute infection.HSV-1 infection induces p35 protein levels. To examine how HSV-1 acute TG infection affects p35, wild-type HSV (KOS)-infected TG were harvested 3 days postinfection, as previously described (24,25). TG sections were immunostained for both the HSV-1 immediate early protein, ICP0, used as a marker for productively infected neurons, and p35. As shown in Fig. 1A, HSV-1-infected neurons showed an increase in p35 staining compared to mock-infected cells, with a distribution that...

show abstract

Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's Sarcoma-associated herpesvirus by herpes simplex virus type 1

Cited by 51 publications

References 45 publications

Transcriptional Analysis of Host Responses to Marek's Disease Virus Infection in Chicken Thymus

Transcriptional Analysis of Host Responses to Marek's Disease Virus Infection in Chicken Thymus

Inhibition of Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication by HIV-1 Nef and Cellular MicroRNA hsa-miR-1258

Herpes Simplex Virus 1 Upregulates p35, Alters CDK-5 Localization, and Stimulates CDK-5 Kinase Activity during Acute Infection in Neurons

Contact Info

Product

Resources

About