• Chikungunya virus
• Coxsackie B virus
• Cytomegalovirus
• FGF2
• FOXG1
• Herpes simplex virus 2
• human
• microcephaly
• neural stem cells
• neurons
• TBK1
• Zika virus

Zika virus (ZIKV) outbreak posed an urgent need to unravel the molecular mechanisms involved of microcephaly induced by neurotropic pathogens of the TORCH group. Here, I aim to investigate the events during TORCH viral infection, using innovative human neural progenitor cells (NPCs) derived from both human fetal neocortex tissue (neuroepithelial stem [NES] cells) and induced pluripotent stem cells (hiPS-NPCs). I focused on two main targets affecting cell cycle progression of NPCs. pTBK1, a kinase involved in the antiviral innate immune response, results delocalized from centrosomes to mitochondria following ZIKV molecular. To verify whether the same mechanism could be involved in other viral infections, I selected four viruses: three TORCH members (Herpes simplex virus, Cytomegalovirus, and Coxsackie B virus) and Chikungunya virus, which is not a TORCH member but it is known to employ the same primary vector of ZIKV and can induce encephalitis and developmental delay. I found that an event at the base of microcephaly etiogenesis is shared by different TORCH and non-TORCH viruses in NES cells and NES cell-derived neurons. Then, I focused on another player involved in NPC proliferation and self-renewal, FOXG1 gene, coding for a forebrain transcription factor and mutations of which are also associated with severe developmental disorders, including microcephaly. Specifically, I investigated ZIKV impact on FOXG1 protein. I found the nuclear displacement and reduction of FOXG1 following infection in hiPS-NPCs. Collectively, our data suggest new potential targets of congenital microcephaly.