ICP0 dismantles microtubule networks in herpes simplex virus-infected cells

Infected-cell protein 0 (ICP0) is a RING finger E3 ligase that regulates herpes simplex virus (HSV) mRNA synthesis, and strongly influences the balance between latency and replication of HSV. For 25 years, the nuclear functions of ICP0 have been the subject of intense scrutiny. To obtain new clues about ICP0's mechanism of action, we constructed HSV-1 viruses that expressed GFP-tagged ICP0. To our surprise, both GFP-tagged and wild-type ICP0 were predominantly observed in the cytoplasm of HSV-infected cells. Although ICP0 is exclusively nuclear during the immediate-early phase of HSV infection, further analysis revealed that ICP0 translocated to the cytoplasm during the early phase where it triggered a previously unrecognized process; ICP0 dismantled the microtubule network of the host cell. A RING finger mutant of ICP0 efficiently bundled microtubules, but failed to disperse microtubule bundles. Synthesis of ICP0 proved to be necessary and sufficient to disrupt microtubule networks in HSV-infected and transfected cells. Plant and animal viruses encode many proteins that reorganize microtubules. However, this is the first report of a viral E3 ligase that regulates microtubule stability. Intriguingly, several cellular E3 ligases orchestrate microtubule disassembly and reassembly during mitosis. Our results suggest that ICP0 serves a dual role in the HSV life cycle, acting first as a nuclear regulator of viral mRNA synthesis and acting later, in the cytoplasm, to dismantle the host cell's microtubule network in preparation for virion synthesis and/or egress

Organizational architecture, ethical culture, and perceived unethical behavior towards customers:Evidence from wholesale banking

In this study, we propose and test a model of the effects of organizational ethical culture and organizational architecture on the perceived unethical behavior of employees towards customers. This study also examines the relationship between organizational ethical culture and moral acceptability judgment, hypothesizing that moral acceptability judgment is an important stage in the ethical decision-making process. Based on a field study in one of the largest financial institutions in Europe, we found that organizational ethical culture was significantly related to the perceived frequency of unethical behavior towards customers and to the moral acceptability judgment of this type of unethical behavior. No support was found for the claim that features of organizational architecture are associated with the perceived frequency of unethical behavior towards customers. This is the first study to document the differential effects of organizational architecture and organizational ethical culture on perceived unethical behavior of employees towards customers, in wholesale banking. Implications for managers and future research are discussed