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- W2559286509 endingPage "2810" @default.
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- W2559286509 abstract "<ns4:p><ns4:italic>Introduction: LCK</ns4:italic>gene, also known as lymphocyte-specific proto-oncogene, is expressed in lymphocytes, and associated with coordinated expression of MHC class I and II in response to physiological stimuli, mediated through a combined interaction of promoters, suppressors, and enhancers. Differential usage of<ns4:italic>LCK</ns4:italic>promoters, transcribes dysfunctional transcript variants leading to leukemogenesis and non-induction of MHC class I gene variants. Viruses use C-type lectins, like<ns4:italic>CD209,</ns4:italic>to penetrate the cell, and inhibit Pattern Recognition Receptors (PRR), hence evading immune destruction. Given that Ebolavirus (EBOV) disease burden could result from a dysfunctional LCK pathway, identification of the genetic pathway leading to proper immune induction is a major priority.<ns4:italic>Methods:</ns4:italic>Data for EBOV related virus samples were obtained from Gene Expression Omnibus database and RMEAN information per gene per sample were entered into a table of values. R software v.3.3.1 was used to process differential expression patterns across samples for<ns4:italic>LCK, CD209</ns4:italic>and immune-related genes. Principal component analysis (PCA) using ggbiplot v.0.55 was used to explain the variance across samples.<ns4:italic>Results:</ns4:italic>Data analyses identified three viral clusters based on transmission patterns as follows:<ns4:italic>LCK-CD209</ns4:italic>dependent, LCK-dependent specific to EBOV, and CD209 dependent. Compared to HLA class II gene variants, HLA class I (A, B and C) variants were <2 fold expressed, especially for EBOV samples. PCA analyses classified<ns4:italic>TYRO3</ns4:italic>,<ns4:italic>TBK1</ns4:italic>and<ns4:italic>LCK</ns4:italic>genes independent of the data, leading to identification of a possible pathway involving<ns4:italic>LCK, IL2, PI3k, TBK1, TYRO3</ns4:italic>and<ns4:italic>MYB</ns4:italic>genes with downstream induction of immune T-cells.<ns4:italic>Discussion</ns4:italic>: This is the first study undertaken to understand the non-functional immune pathway, leading to EBOV disease pathogenesis and high fatality rates. Our lab currently exploits, through cutting edge genetic technology to understand the interplay of identified genes required for proper immune induction. This will guide antiviral therapy and possible markers for viral disease identification during outbreaks.</ns4:p>" @default.
- W2559286509 created "2016-12-08" @default.
- W2559286509 creator A5037031175 @default.
- W2559286509 creator A5043326989 @default.
- W2559286509 creator A5045714267 @default.
- W2559286509 creator A5057327954 @default.
- W2559286509 creator A5082768602 @default.
- W2559286509 date "2016-12-02" @default.
- W2559286509 modified "2023-09-26" @default.
- W2559286509 title "Identification of genetic pathways driving Ebola virus disease in humans and targets for therapeutic intervention" @default.
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