HCMV infection of NPCs results in the loss of the SOX2 protein
Congenital human cytomegalovirus (HCMV) infection is the leading cause of birth defects worldwide. Approximately 1% of live newborns are infected in utero with this virus. Recent advances in human neural progenitor cell (NPC) isolation and culture have provided an opportunity to study HCMV infection in a cell system relevant to fetal neuropathogenesis.
In a recent report, the research group led by Prof. LUO Minhua in Wuhan Institute of Virology of the Chinese Academy of Sciences investigated the effects of HCMV infection on SOX2 expression in human NPCs. They demonstrated that the HCMV 72-kDa immediate-early 1 (IE1) protein down regulates SOX2 transcription and mediates depletion of the SOX2 protein from HCMV- infected NPCs. IE1 exerts its effect on SOX2 expression by inactivating the upstream regulator STAT3.
In this study, the scientists reported that the HCMV proteins known as IE1 and IE2 target expression of human SOX2, a central pluripotency-associated transcription factor that governs neural progenitor cell (NPC) fate and is required for normal brain development. Both during HCMV infection and when expressed alone, IE1 causes the loss of SOX2 from NPCs. IE1 mediates SOX2 depletion by targeting STAT3, a critical upstream regulator of SOX2 expression.
In summary, this study initially links the interaction between IE1 and STAT3 to SOX2 depletion and thereby identifies a novel pathway predicted to contribute to developmental neuropathogenesis caused by congenital HCMV infection.
The results have been published in Journal of Virology entitled "Human Cytomegalovirus Immediate-Early 1 Protein Causes Loss of SOX2 from Neural Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus ".
This work was supported by the Ministry of Science and Technology of China, the National Natural Science Foundation of China, the Sino-Africa Joint Research Centre, a seed grant from the University of Idaho, the Wellcome Trust Institutional Strategic Support Fund, the Medical Research Council and Tenovus Scotland, and the Deutsche Forschungsgemeinschaft.
HCMV infection down-regulates SOX2 at the mRNA and protein level in NPCs. Image by LUO Minhua
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China (http://english.whiov.cas.cn/)