Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections

CCZ1 is a guanine nucleotide exchange factor involved in endolysosomal trafficking of viruses. Haploid murine embryonis stem cells were subjected to transposon mutagenesis  so as to identify genes essential for filoviruses infection. The knockout of CCZ1 from both halploid and diploid cells resulted in a significant drop in infection by the vesicular stomatitis virus pseudotyped with the Marburg virus glycoprotein, confirming its importance in the entry of filoviruses into cells. In addition, the knockout of both CCZ1 and RAB7 results into a complte resistance to Marburg virus  infection in human cells. The CCZ1 knockdown in human hepatocytes and human blood-vessel organoidsalso resulted in  reduction in viral infection. The role of CCZ1 in endosomal trafficking ahead of lysosomal fusion was also confirmed. Ccz1 is also involved in the entro of SARS-CoV-2 infection through the endosomal pathway, but is not involved in Lassa viruses. Hence, CCZ1 is a potential target for drugs targeting viral infections caused by Marburg, ebola and sars-cov-2 viruses.
(MRM)