title: Post HCV Infection Due to MX Gene Stimulation Produced Post Treatment with Imported and Locally Produced Egyptian Biosimilar IFN.
abstract: BACKGROUND
  Cirrhosis is regarded as a possible end stage of many liver diseases, including viral infection. It occurs when healthy liver tissue becomes damaged and is replaced by scar tissue and finally may lead to hepatocellular carcinoma. Interferons (IFNs)are two general categories, type I and II. Type I includes one beta interferon and over 20 different alpha interferons. Alpha interferons are very similar in how they work, interacting with other proteins on cells like receptors. The main objective of this study was to compare Mx gene productivity post different cell line treatment with imported and Egyptian biosimilar locally produced IFNs, as well as the efficacy of those tested IFNs. Also, an assessment was made of sensitivity of different cell lines as alternatives to that recommended for evaluation of antiviral activity.
  
  
  METHODS
  Different cell lines (Vero, MDBK and Wish) were employed to evaluate cytotoxicity using the MTT assay. Antiviral activity was evaluated compared with standard IFN against VSV, Indiana strain -156, on tested rh-IFNs (imported; innovated and Egyptian biosimilar locally produced IFNs) in the pre-treated cell lines previously mentioned. The virus was propagated in the Wish cell line as recommended. Finally we estimated up-regulation of the Mx gene as a biomarker.
  
  
  RESULTS
  Data recorded revealed that test IFNs were safe in test cell lines. Viability was around 100%. Locally tested interferon did not realize the international potency limits, while the imported one was accepted compared with the standard IFN. These results were the same either using infectivity titer reduction assay or crystal violet staining of residual non- infected cells. Mx protein production was cell type related and confirmed by the detected Mx gene expressed in imported and locally produced IFN pre-treated cell lines. The expression of the gene was arranged in the order of Vero> wish > MDBK for the imported IFN, while for the Egyptian biosimillar locally produced one it was MDBK>Vero> wish. With regard to the antiviral activity there was a significant difference of imported IFN potency compared with the locally produced IFN (P<0.05), the IFN potential (antiviral activity) was not cell line related and showed non-significant difference for each separate product.
  
  
  CONCLUSIONS
  Vero cells can be used as an alternative cell line for evaluation of IFN potency in case of unavailable USP recommended cell lines. Alternative potency evaluation assay could be used and proved significant difference in IFN potency in case of local and imported agents. Evaluation of antiviral activity could be used in parallel to viral infectivity reduction assay for better accuracy. Mx gene can be used as a marker for IFN potential.
authors: National Organization for Research and Control of Biological (NORCB), Dokki, Giza, Egypt E-mail : phshereenhamdy@gmail.com.
authors: Shereen H
authors: SH
authors: Mohamed
authors: Nora F
authors: NF
authors: Mahmoud
authors: Aly F
authors: AF
authors: Mohamed
authors: Nahla S
authors: NS
authors: Kotb
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001681:Biological Assay / Q000379:methods; D059451:Biosimilar Pharmaceuticals / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004534:Egypt; D015870:Gene Expression; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D007372:Interferons / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology*; D064547:Myxovirus Resistance Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015854:Up-Regulation; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D059451:Biosimilar Pharmaceuticals; D064547:Myxovirus Resistance Proteins; D007372:Interferons