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Role of HCV Core gene of genotype 1a and 3a and host gene Cox-2 in HCV-induced pathogenesis.
Virol J. 2011 Apr 01; 8:155.VJ

Abstract

BACKGROUND

Hepatitis C virus (HCV) Core protein is thought to trigger activation of multiple signaling pathways and play a significant role in the alteration of cellular gene expression responsible for HCV pathogenesis leading to hepatocellular carcinoma (HCC). However, the exact molecular mechanism of HCV genome specific pathogenesis remains unclear. We examined the in vitro effects of HCV Core protein of HCV genotype 3a and 1a on the cellular genes involved in oxidative stress and angiogenesis. We also studied the ability of HCV Core and Cox-2 siRNA either alone or in combination to inhibit viral replication and cell proliferation in HCV serum infected Huh-7 cells.

RESULTS

Over expression of Core gene of HCV 3a genotype showed stronger effect in regulating RNA and protein levels of Cox-2, iNOS, VEGF, p-Akt as compared to HCV-1a Core in hepatocellular carcinoma cell line Huh-7 accompanied by enhanced PGE2 release and cell proliferation. We also observed higher expression levels of above genes in HCV 3a patient's blood and biopsy samples. Interestingly, the Core and Cox-2-specific siRNAs down regulated the Core 3a-enhanced expression of Cox-2, iNOS, VEGF, p-Akt. Furthermore, the combined siRNA treatment also showed a dramatic reduction in viral titer and expression of these genes in HCV serum-infected Huh-7 cells. Taken together, these results demonstrated a differential response by HCV 3a genotype in HCV-induced pathogenesis, which may be due to Core and host factor Cox-2 individually or in combination.

CONCLUSIONS

Collectively, these studies not only suggest a genotype-specific interaction between key players of HCV pathogenesis but also may represent combined viral and host gene silencing as a potential therapeutic strategy.

Authors+Show Affiliations

Applied and Functional Genomics Laboratory, National Centre of Excellence in Molecular Biology, University of Punjab, Lahore 53700, Pakistan. sajihassan2004@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21457561

Citation

Jahan, Shah, et al. "Role of HCV Core Gene of Genotype 1a and 3a and Host Gene Cox-2 in HCV-induced Pathogenesis." Virology Journal, vol. 8, 2011, p. 155.
Jahan S, Khaliq S, Ijaz B, et al. Role of HCV Core gene of genotype 1a and 3a and host gene Cox-2 in HCV-induced pathogenesis. Virol J. 2011;8:155.
Jahan, S., Khaliq, S., Ijaz, B., Ahmad, W., & Hassan, S. (2011). Role of HCV Core gene of genotype 1a and 3a and host gene Cox-2 in HCV-induced pathogenesis. Virology Journal, 8, 155. https://doi.org/10.1186/1743-422X-8-155
Jahan S, et al. Role of HCV Core Gene of Genotype 1a and 3a and Host Gene Cox-2 in HCV-induced Pathogenesis. Virol J. 2011 Apr 1;8:155. PubMed PMID: 21457561.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of HCV Core gene of genotype 1a and 3a and host gene Cox-2 in HCV-induced pathogenesis. AU - Jahan,Shah, AU - Khaliq,Saba, AU - Ijaz,Bushra, AU - Ahmad,Waqar, AU - Hassan,Sajida, Y1 - 2011/04/01/ PY - 2010/12/01/received PY - 2011/04/01/accepted PY - 2011/4/5/entrez PY - 2011/4/5/pubmed PY - 2011/8/9/medline SP - 155 EP - 155 JF - Virology journal JO - Virol. J. VL - 8 N2 - BACKGROUND: Hepatitis C virus (HCV) Core protein is thought to trigger activation of multiple signaling pathways and play a significant role in the alteration of cellular gene expression responsible for HCV pathogenesis leading to hepatocellular carcinoma (HCC). However, the exact molecular mechanism of HCV genome specific pathogenesis remains unclear. We examined the in vitro effects of HCV Core protein of HCV genotype 3a and 1a on the cellular genes involved in oxidative stress and angiogenesis. We also studied the ability of HCV Core and Cox-2 siRNA either alone or in combination to inhibit viral replication and cell proliferation in HCV serum infected Huh-7 cells. RESULTS: Over expression of Core gene of HCV 3a genotype showed stronger effect in regulating RNA and protein levels of Cox-2, iNOS, VEGF, p-Akt as compared to HCV-1a Core in hepatocellular carcinoma cell line Huh-7 accompanied by enhanced PGE2 release and cell proliferation. We also observed higher expression levels of above genes in HCV 3a patient's blood and biopsy samples. Interestingly, the Core and Cox-2-specific siRNAs down regulated the Core 3a-enhanced expression of Cox-2, iNOS, VEGF, p-Akt. Furthermore, the combined siRNA treatment also showed a dramatic reduction in viral titer and expression of these genes in HCV serum-infected Huh-7 cells. Taken together, these results demonstrated a differential response by HCV 3a genotype in HCV-induced pathogenesis, which may be due to Core and host factor Cox-2 individually or in combination. CONCLUSIONS: Collectively, these studies not only suggest a genotype-specific interaction between key players of HCV pathogenesis but also may represent combined viral and host gene silencing as a potential therapeutic strategy. SN - 1743-422X UR - https://www.unboundmedicine.com/medline/citation/21457561/Role_of_HCV_Core_gene_of_genotype_1a_and_3a_and_host_gene_Cox_2_in_HCV_induced_pathogenesis_ L2 - https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-8-155 DB - PRIME DP - Unbound Medicine ER -