Faculty Collaboration Database

Inhibition of cellular STAT3 synergizes with the cytomegalovirus kinase inhibitor maribavir to disrupt infection. Antiviral Res 2013 Nov;100(2):321-7

Date

09/28/2013

Pubmed ID

24070820

Pubmed Central ID

PMC3845884

DOI

10.1016/j.antiviral.2013.09.011

Scopus ID

2-s2.0-84885352457 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

Therapeutic strategies controlling human cytomegalovirus (hCMV) infection are limited due to adverse side effects and emergence of antiviral resistance variants. A compound being evaluated for treating hCMV disease is maribavir (MBV) which disrupts replication by inhibiting the viral kinase pUL97. Previous studies have demonstrated that the antiviral activity of MBV is sensitive to the proliferation state of the infected cell. In these studies, we were interested in determining whether inhibition of the pro-proliferative transcription factor, signal transducer and activator of transcription-3 (STAT3), could influence the antiviral activity of MBV. The addition of the STAT3 inhibitor, S3i-201, during infection altered hCMV-mediated changes in cell cycle protein expression. Upon combining S3i-201 with MBV, our data suggest that STAT3 inhibition is acting synergistically with MBV to inhibit infection in vitro. Furthermore, specific concentrations of S3i-201 and MBV induced caspase-dependent death of infected but not uninfected cell. Our studies suggest that treating infection with both S3i-201 and MBV is a novel approach to inhibit hCMV replication.

Author List

Reitsma JM, Terhune SS

Author

Scott Terhune PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aminosalicylic Acids
Antiviral Agents
Benzenesulfonates
Benzimidazoles
Cell Line
Cytomegalovirus
Drug Synergism
Humans
Ribonucleosides
STAT3 Transcription Factor
Virus Replication