AIMS: To investigate the myxovirus-resistance protein A (MxA) and double-stranded RNA-activated protein kinase (PKR) genetic response to interferon (IFN) therapy in hepatitis C virus (HCV) genotype 4-infected patients. Moreover, we studied the association between suppressor of cytokine signaling 3 (SOCS3) gene expression and therapy resistance in genotype 4. Finally, we investigated the novel link between p53 and IFN-stimulated genes (ISGs) in humans. METHODS: Gene expression analyses were performed in peripheral blood using TaqMan real-time PCR. Virologic response was assessed with a branched-DNA assay. Genotyping was confirmed. RESULTS: Early virologic responders (EVRs, n = 23) but not non-EVRs (n = 7) showed strong upregulation of PKR at week 12 of therapy compared to baseline. Both EVRs and non-EVRs showed MxA upregulation at week 12 compared to baseline. Baseline SOCS3 expression did not distinguish EVRs from non-EVRs in genotype 4. An association was found between p53 and MxA and PKR gene expression. CONCLUSION: Measurement of MxA and PKR transcriptional induction during treatment may distinguish EVRs from non-EVRs in genotype 4. SOCS3 gene does not seem to be implicated in therapy resistance in genotype 4. An association between p53 and ISGs expression was shown for the first time in HCV-infected patients, further supporting the contribution of p53 to host antiviral response.
AIMS: To investigate the myxovirus-resistance protein A (MxA) and double-stranded RNA-activated protein kinase (PKR) genetic response to interferon (IFN) therapy in hepatitis C virus (HCV) genotype 4-infected patients. Moreover, we studied the association between suppressor of cytokine signaling 3 (SOCS3) gene expression and therapy resistance in genotype 4. Finally, we investigated the novel link between p53 and IFN-stimulated genes (ISGs) in humans. METHODS: Gene expression analyses were performed in peripheral blood using TaqMan real-time PCR. Virologic response was assessed with a branched-DNA assay. Genotyping was confirmed. RESULTS: Early virologic responders (EVRs, n = 23) but not non-EVRs (n = 7) showed strong upregulation of PKR at week 12 of therapy compared to baseline. Both EVRs and non-EVRs showed MxA upregulation at week 12 compared to baseline. Baseline SOCS3 expression did not distinguish EVRs from non-EVRs in genotype 4. An association was found between p53 and MxA and PKR gene expression. CONCLUSION: Measurement of MxA and PKR transcriptional induction during treatment may distinguish EVRs from non-EVRs in genotype 4. SOCS3 gene does not seem to be implicated in therapy resistance in genotype 4. An association between p53 and ISGs expression was shown for the first time in HCV-infectedpatients, further supporting the contribution of p53 to host antiviral response.
Authors: Brittany E Yee; Nghia H Nguyen; Bing Zhang; Philip Vutien; Carrie R Wong; Glen A Lutchman; Mindie H Nguyen Journal: Eur J Gastroenterol Hepatol Date: 2014-11 Impact factor: 2.566
Authors: Alexander V Kofman; Christopher Letson; Evan Dupart; Yongde Bao; William W Newcomb; David Schiff; Jay Brown; Roger Abounader Journal: Med Hypotheses Date: 2013-05-02 Impact factor: 1.538
Authors: Brittany E Yee; Nghia H Nguyen; Bing Zhang; Derek Lin; Philip Vutien; Carrie R Wong; Glen A Lutchman; Mindie H Nguyen Journal: BMJ Open Gastroenterol Date: 2015-07-09