Tachypleus tridentatus Lectin Enhances Oncolytic Vaccinia Virus Replication to Suppress In Vivo Hepatocellular Carcinoma Growth

Mar Drugs. 2018 Jun 7;16(6):200. doi: 10.3390/md16060200.

Abstract

Lectins play diverse roles in physiological processes as biological recognition molecules. In this report, a gene encoding Tachypleus tridentatus Lectin (TTL) was inserted into an oncolytic vaccinia virus (oncoVV) vector to form oncoVV-TTL, which showed significant antitumor activity in a hepatocellular carcinoma mouse model. Furthermore, TTL enhanced oncoVV replication through suppressing antiviral factors expression such as interferon-inducible protein 16 (IFI16), mitochondrial antiviral signaling protein (MAVS) and interferon-beta (IFN-β). Further investigations revealed that oncoVV-TTL replication was highly dependent on ERK activity. This study might provide insights into a novel way of the utilization of TTL in oncolytic viral therapies.

Keywords: ERK; TTL; oncolytic vaccinia virus; viral replication.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / pharmacology
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / virology
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • DNA Replication / drug effects
  • HEK293 Cells
  • Horseshoe Crabs / metabolism*
  • Humans
  • Interferon-beta / metabolism
  • Lectins / pharmacology*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / virology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oncolytic Virotherapy / methods
  • Oncolytic Viruses / drug effects*
  • Phosphoproteins / metabolism
  • Vaccinia virus / drug effects
  • Virus Replication / drug effects*

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Lectins
  • Phosphoproteins
  • Interferon-beta