A novel role of syntaxin 3 as a regulator of human cytomegalovirus gene expression

Abstract

As an enveloped virus, HCMV exploits intracellular membranes for its assembly and release. We recently reported that HCMV induces the expression of the SNARE protein Syntaxin 3 (Stx3), which is required for virus production through a mechanism that involves late endosomes. Moreover, we have found that Stx3 mono-ubiquitination targets it to this compartment. Here we show that overexpression of a non-ubiquitinated Stx3 mutant (Stx3-5R) strongly inhibits infectious virus production. Stx3-5R not only reduced the expression of HCMV structural and non-structural proteins but also delayed the expression of the immediate-early gene product EA1. Using qPCR we found that transcript levels of the essential viral transactivators EA1 and EA2 were also reduced in the presence of Stx3-5R. We are currently studying the molecular mechanism that underlay this downregulation. Based on this we propose a novel role for Stx3 as a regulator of HCMV gene expression.