Targeting the human TREX complex to prevent herpesvirus replication: what is new?


Like all viruses, herpesviruses manipulate and utilize the host cell’s machinery to enhance their own replication to produce infectious virions, resulting in virus spread and disease. One such example, essential for herpesvirus replication, is the interaction of a conserved family of herpesvirus-encoded RNA-binding proteins with a large cellular multiprotein complex termed TREX [6–10]. Human herpesviruses utilize multiple components of hTREX to stabilize and thus preferentially promote nuclear export of herpesviral mRNAs [11]. Specifically, hTREX serves as a binding platform for the cellular mRNA export factor Nxf1 on herpesvirus mRNAs forming a stable and export competent viral ribonucleoprotein particle.

The recent discovery that a core component of hTREX, the RNA helicase UAP56, remodels the hTREX complex in an ATP-dependent manner [12,13] has given rise to the idea that the interaction of hTREX with herpesvirus-encoded adapter proteins might also be regulated in an ATP-dependent manner. This strategy provided an especially attractive option for inhibition of herpesvirus replication, as targeting of the ATPase function of viral and cellular RNA helicases has already been explored, showing selective pharmacological targeting is possible [14–16]. Notably, the targeting of a cellular RNA helicase would also reduce the risk of viral resistance and would have potential pan-herpesvirus activity.

Read the full article in Future Virology here.


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