High Mobility Group Box 1 Influences HSV1716 Spread and Acts as an Adjuvant to Chemotherapy.

Abstract

High Mobility Group Box 1 (HMGB1) is a multifunctional protein that plays various roles in the processes of inflammation, cancer, and other diseases. Many reports document abundant HMGB1 release following infection with oncolytic viruses (OVs). Further, other groups including previous reports from our laboratory highlight the synergistic effects of OVs with chemotherapy drugs. Here, we show that virus-free supernatants have varying cytotoxic potential, and HMGB1 is actively secreted by two established fibroblast cell lines (NIH 3T3 and 3T6-Swiss albino) following HSV1716 infection in vitro. Further, pharmacologic inhibition or genetic knock-down of HMGB1 reveals a role for HMGB1 in viral restriction, the ability to modulate bystander cell proliferation, and drug sensitivity in 3T6 cells. These data further support the multifactorial role of HMGB1, and suggest it could be a target for modulating the efficacy of oncolytic virus therapies alone or in combination with other frontline cancer treatments.

• Authors: Leslee Sprague, Joel M Lee, Brian J Hutzen, Pin-Yi Wang, Chun-Yu Chen, Joe Conner, Lynne Braidwood, Kevin A Cassady, Timothy P Cripe
• Journal: Viruses (Viruses) Vol. 10 Issue 3 (03 15 2018) ISSN: 1999-4915 [Electronic] Switzerland
• PMID: 29543735 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Conditioned
• HMGB1 Protein

Topics

• Animals
• Bystander Effect (drug effects)
• Cell Line
• Cell Proliferation (drug effects)
• Culture Media, Conditioned (pharmacology)
• Gene Knockdown Techniques
• HMGB1 Protein (genetics, metabolism)
• Herpes Simplex (drug therapy, metabolism, virology)
• Humans
• Mice
• NIH 3T3 Cells
• Oncolytic Viruses (physiology)
• Simplexvirus (drug effects, physiology)
• Virus Replication (drug effects)