AI Article Synopsis

  • Hepatitis C virus (HCV) enters liver cells using common pathways, making host factors like human occludin (hOCLN) potential targets for treatment.
  • A new monoclonal antibody called 67-2 was created to target the second extracellular loop of hOCLN, effectively blocking HCV infection in a specific human liver cell line.
  • The 67-2 antibody was found to interact with both human and mouse occludin, suggesting it recognizes a conserved feature, and it did not harm cell viability or tight junction function.

Article Abstract

Since hepatitis C virus (HCV) is thought to enter into host hepatocytes using the same cellular pathways regardless of the genotypes, the host factors are promising targets to prevent and treat HCV infection. Human occludin (hOCLN) is one representative entry factor, and its second extracellular loop (EC2) contributes to the species selectivity of HCV-susceptibility. However, the exact function of hOCLN during HCV entry remains unknown, and no hOCLN-targeting antibodies or synthetic drugs that prevent and treat HCV infection have yet been developed. Here we generated the anti-hOCLN-EC2 monoclonal antibody (mAb) 67-2, and demonstrated that it efficiently inhibited HCV infection in the HCV-permissive human cell line Huh7.5.1. We also showed, using three different culture systems of Huh7.5.1 cells, that this novel mAb is accessible to OCLN from the basolateral side of hepatocytes but not from the apical side. In addition, our Western blot analyses indicated that the established 67-2 mAb reacted not only with hOCLN but also with mouse OCLN, strongly suggesting that 67-2 does not recognize the human-specific amino acids in OCLN-EC2. Moreover, we revealed that the anti-hOCLN-EC2 mAb 67-2 showed no adverse effects on cell viability or the barrier function of tight junctions.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908272PMC
http://dx.doi.org/10.18632/oncotarget.24742DOI Listing

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