Subcellular quantitative proteomic analysis reveals host proteins involved in human cytomegalovirus infection

• First subcellular proteomic analysis on nucleus and cytoplasm of HCMV infected cells
• A global view of proteome of HCMV-infected HEL cells was profiled.
• Functional analysis indicated five regulated proteins can influence HCMV replication.
• Our study suggests UB2V2, PHB2 and HNRPD as potential targets for anti-HCMV study.

Viral replication requires host cell macromolecules and energy, although host cells can alter their protein expression to restrict viral replication. To study the host cell response to human cytomegalovirus (HCMV) infection, a stable isotope labeling by amino acids in cell culture (SILAC)-based subcellular quantitative proteomic study of HCMV-infected human embryo lung fibroblast (HEL) cells was performed, and a total of 247 host proteins were identified as differentially regulated by HCMV. Western blotting and immunofluorescence confocal microscopy were performed to validate the data sets. Gene Ontology analysis indicated that cellular processes involving the metabolism, localization and immune system were regulated as a result of HCMV infection. Functional analysis of selected regulated proteins revealed that knockdown of HNRPD, PHB2 and UB2V2 can increase HCMV replication, while knockdown of A4 and KSRP resulted in decreased HCMV replication. Our study may improve our understanding of the dynamic interactions between HCMV and its host and provide multiple potential targets for anti-HCMV agent research.