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Cytokine interactome alterations promote oropharyngeal Epstien-barr virus (EBV) replication and shedding during HIV infection

ABSTRACT: Proteomic analysis of cytokines in unstimulated oropharyngeal secretions. Epstein-barr virus (EBV) is a type 1 carcinogen which causes many cancers in humans. Here we explored the cytokine involvement of the EBV replication process in the oropharynx. Cytokine interactomic profiles were geneerated to understand the involved signalling pathways in HIV infected group and the healthy group. Proteome profilers were used to understand the major cytokine expression levels that are related to infection and immune regulation. We analyzed unstimulated oropharyngeal samples (UOPS) from 42 healthy subjects and 72 HIV positive subjects using the R & D Proteome Profiler array panels. No techinical replicates were performed. 14 samples in HIV group without therapy (NHAART group); 58 HIV patients with highly active antiretroviral therapy (HAART group); 42 samples in healthy group

ORGANISM(S): Homo Sapiens

SUBMITTER: K H Chan R A Perera C S Tsang R A P M Perera M P Lee P Li C S Miller L P Samaranayake

PROVIDER: E-GEOD-21339 | ArrayExpress | 2010-04-15

SECONDARY ACCESSION(S): GSE21339PRJNA126155

REPOSITORIES: GEO, ArrayExpress

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Project description:A growing number of studies reveal that oxidative stress is associated with viral infections or cancer development. However, there are few reports assessing the relationships between oxidative stress, viral infection, and carcinogenesis. The present study analyzed the level of total antioxidant status (TAS) as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in patients with oropharyngeal cancer both Epstein-Barr virus (EBV)-positive and EBV-negative in comparison with the control group. The correlations between these parameters and EBV type (wild-type LMP1 (wt-LMP1) or LMP1 with deletion (del-LMP1)), level of antibodies against EBV, the degree of tumor differentiation, and TNM classification were also investigated. Fresh frozen tumor tissue samples collected from 66 patients with oropharyngeal squamous cell carcinoma were tested using nested PCR assay for EBV DNA detection. Spectrophotometric methods were used to measure TAS values as well as SOD and GPx activities in homogenates of tissue, using diagnostic kits produced by Randox Laboratories. Sera from all individuals were investigated using ELISA method to detect the presence of Epstein-Barr virus capsid antigen (EBVCA) IgM and IgG, Epstein-Barr virus nuclear antigen (EBNA) IgG, and early antigen (EA) IgG antibodies. The level of TAS and activities of antioxidant enzymes (GPx and SOD) were significantly decreased in tissues with oropharyngeal cancer, particularly in EBV-positive cases. In 82.3% of patients, wt-LMP1 was detected. Significantly lower TAS, GPx, and SOD values were stated in patients infected with wild-type EBV. The presence of antibodies against early antigen (anti-EA) was detected in over 80% of patients, which suggests reactivation of EBV infection. The correlation between the degree of tumor differentiation and TN classification, especially in EBV-positive patients, was also observed. Determination of these parameters may be useful in evaluating tumor burden in patients with various stages of oropharyngeal cancer and could be an important prognostic factor. Future studies are needed to understand the role of EBV lytic reactivation induced by oxidative stress.

			Action	DRS
	E-GEOD-21339.README.txt	Txt
	E-GEOD-21339.idf.txt	Idf
	E-GEOD-21339.processed.1.zip	Processed
	E-GEOD-21339.sdrf.txt	Txt

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Cytokine interactome alterations promote oropharyngeal Epstien-barr virus (EBV) replication and shedding during HIV infection

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