Human Cytomegalovirus Exploits Interferon-induced Transmembrane Proteins To Facilitate Morphogenesis Of The Virion Assembly Compartment

Recently, interferon-induced transmembrane proteins(IFITMs) have been identified as key effector molecules in the host type I interferon defense system. The invasion of host cells by a large range of RNA viruses is inhibited by IFITMs during the entry step. However, the roles of IFITMs in DNA virus infections have not been studied in detail. In this study, we report that human cytomegalovirus(HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment(vAC) during the infection of human fibroblasts. We found that IFITMs were expressed constitutively in human embryonic lung fibroblasts(MRC5). HCMV infection inhibited IFITM protein accumulation in the later stages of infection. Overexpression of an IFITM protein in MRC5 cells slightly enhanced HCMV production and RNAi knockdown of IFITMs reduced the virus titer by about 100-fold on day 8 post-infection according to a multi-step growth assays. Virus gene expression and DNA synthesis were not affected, but the typical round structure of vAC was not formed after the suppression of IFITMs, thereby resulting in defective virion assembly and the production of less infectious virion particles. Interestingly, the replication of herpes simplex virus, a human herpesvirus that is related closely to HCMV, was not affected by the suppression of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a specific pathway required for HCMV replication.