Wedelolactone inhibits human cytomegalovirus replication by targeting distinct steps of the viral replication cycle

Svrlanska A, Ruhland A, Marschall M, Reuter N, Stamminger T (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Antiviral Research Elsevier Masson

Book Volume: 174

Article Number: 104677

DOI: 10.1016/j.antiviral.2019.104677

Abstract

Wedelolactone (WDL) is a coumestan present in the plants Eclipta prostrata and Wedelia calendulacea which are used for treatment of a multitude of health problems in traditional medicine. It has previously been shown that WDL exerts antiviral activity against human immunodeficiency virus and hepatitis C virus. In this study, we investigated the effect of WDL on lytic human cytomegalovirus (HCMV) infection. We demonstrate a strong interference with HCMV replication as analyzed in multi-round replication settings. A more detailed analysis of the underlying mechanisms revealed that WDL acts at two distinct steps of the viral replication cycle. During immediate early (IE) times, we observe an inhibition of IE1/IE2 expression. Although WDL was reported to interfere with NF-κB signaling our results suggest the existence of additional mechanisms that impede viral IE expression. During later time points of infection, WDL induced a disruption of the interaction between EZH2 and EED, components of the virus-supportive polycomb repressive complex 2 (PRC2). Thereby, the stability of the PRC2 complex as well as the related complex PRC1 was disturbed leading to diminished viral DNA synthesis. Taken together, we identify WDL as a potent agent against HCMV which interferes at two distinct steps of viral replication.

Authors with CRIS profile

Adriana Svrlanska Professur für Mikrobiologie Manfred Marschall Medizinische Fakultät

Involved external institutions

Universitätsklinikum Ulm DE Germany (DE)

How to cite

APA:

Svrlanska, A., Ruhland, A., Marschall, M., Reuter, N., & Stamminger, T. (2020). Wedelolactone inhibits human cytomegalovirus replication by targeting distinct steps of the viral replication cycle. Antiviral Research, 174. https://dx.doi.org/10.1016/j.antiviral.2019.104677

MLA:

Svrlanska, Adriana, et al. "Wedelolactone inhibits human cytomegalovirus replication by targeting distinct steps of the viral replication cycle." Antiviral Research 174 (2020).

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