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Scientists Identify IE1 as the First Potential HCMV-encoded E3 Ubiquitin Ligase

Aug 14, 2017

Congenital human cytomegalovirus (HCMV) infection is one of the most common causes of neurological disabilities in children. However, the relationship between Hes1 regulation and virus infection, in particular whether and how HCMV regulates Hes1, remained unknown.  

In the present study, the research group led by Prof. LUO Minhua from Wuhan Institute of Virology of the Chinese Academy of Sciences report for the first time that HCMV infection downregulates Hes1 protein at the level in human NPCs through IE1 via a newly identified function, which may be a key mechanism that contributes to fetal brain maldevelopment caused by congenital HCMV infection. 

The scientists demonstrated that HCMV infection downregulates Hes1 protein levels in infected human NPCs. Importantly, IE1 leads to Hes1 depletion by mediating Hes1 ubiquitination and proteasomal degradation by acting as a potential E3 ubiquitin ligase. IE1 physically interacts with Hes1 via amino acids (AA) 451–475, which are also essential for IE1-mediated Hes1 ubiquitination.  

In addition, Sp100A, an important component of PML nuclear bodies (PML-NBs), is identified as an additional ubiquitination substrate of IE1 ubiquitination.  

This study not only suggests an important mechanism for fetal brain development disorders induced by congenital HCMV infection, but also reveals a novel unanticipated function of HCMV IE1 as a potential E3 ubiquitin ligase. 

The results have been published in PloS Pathogens entitled "Human cytomegalovirus IE1 downregulates Hes1 in neural progenitor cells as a potential E3 ubiquitin ligase".  

This work was supported by the National Natural Science Foundation of China and the National Basic Research Program of China (973 Program).   

 

The IE1/Hes1 interaction requires AA451-475 of IE1 (Image by LUO Minhua) 

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