Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiles in individuals with asymptomatic infections against cognate household members with dengue fever

ABSTRACT: Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflict ~50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue largely remain unnoticed. The immune correlates conferring protection to individuals that remain clinically asymptomatic have seldom been investigated. We determined the gene expression profiles of host immune factors in individuals with asymptomatic infections, and whose cognate household members showed symptoms and signs consistent to clinical dengue infection. Results provide insight in association of certain host genes to protection against clinical dengue. Blood samples were collected from Dengue Fever (DF) and Dengue Haemorrhagic Fever (DHF) patients in Malaysia who were admitted to university of Malaya Medical Centre (UMMC), Ampang Hospital (AmpangHospital), and Hospital Tengku Ampuan Rahimah (HTAR) Klang. Blood from their asymptomatic household members were also collected. Their peripheral blood mononuclear cells (PBMCs) were isolated. 29 sample pairs (SP) of dengue patients and their accompanying asymptomatic household members were chosen on the following basis for two-channel microarray experiments: patients who have shown positive results for DENV infection with at least 2 diagnostics tests indicating positivity. Positive results for the IgM-captured ELISA were P/N ratio more than 2.0, while total antibody titer of more than 1:2560 or 4 fold increase from acute to convalescence phase was considered positive in HI assay. PRNT, a neutralization test, was used as a measure for levels of neutralizing antibodies and was considered high when it was more than 1:640, based on a reduction neutralization of 50%.

ORGANISM(S): Homo sapiens

SUBMITTER: Shamala Sekaran

PROVIDER: E-GEOD-50634 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The COP9 signalosome (CSN) is a conserved protein complex occurring in all eukaryotes. The mammalian CSN consists of eight subunits (CSN1 – CSN8) and possesses an intrinsic metalloprotease JAMM motif localised to CSN5. In addition, it is associated with kinases such as protein kinase CK2 and D and the ubiquitin (Ub) specific protease 15. It regulates cullin-RING Ub ligases (CRLs) that label proteins for proteolysis with poly-Ub chains in the Ub proteasome system (UPS). CRLs contain one of the scaffolding cullins 1 – 7, a RING domain protein e. g. Rbx1, and one of hundreds of substrate binding units such as F-box or BTB proteins that specifically target proteins for ubiquitination. The CSN forms functional supercomplexes with CRLs. It removes the Ub-like protein Nedd8 from cullins by its metalloprotease activity and thereby inactivates CRLs. On the other hand, it is essential for CRL function by protecting components and allowing reassembly of the complexes. As a regulator of the UPS the CSN is involved in cell cycle10, DNA repair and development. Overexpression of CSN subunits has been reported in tumour cells. Up to date nothing is known about CSN biogenesis and its regulation. Ten years ago we have observed that overexpression of selected CSN subunits caused a coordinated increase of all CSN subunits and a de novo biosynthesis of the entire complex. Here we show that overexpression of CSN1 mediates an increase of c-Myc which coordinates CSN subunit expression via microRNAs (miRNAs). miRNAs are evolutionarily conserved, endogenous, small, noncoding RNA molecules of about 22 nucleotides that function as posttranscriptional gene regulators. We found that inhibitors of let-7 family miRNAs or upregulation of c-Myc, which represses let-7 miRNAs, resulted in a coordinated increase of CSN subunits and de novo CSN biogenesis. Keywords: Gene expression analysis of human RNA samples using topic-defined PIQOR™ Ubiquitin-PS Microarrays. Two different platforms were used (these are two different microarray batches which are identical in terms of the spotted cDNAs, but differ in the position of some cDNAs) Gene expression analysis of Hela cells overexpressing either CSN2 or CSN1 was performed to study CSN biogenesis and its regulation. Curcumin, Nr. 8 (Curcumin analogon) and Piceatannol were used for the treatment of Hela cells since they inhibit the CSN associated kinases. The aim was to investigate the effect on the signalosome. For each treatment 50 µM Curcumin, Nr. 8 and Piceatannol were used.

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Gene expression profiles in individuals with asymptomatic infections against cognate household members with dengue fever

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