A Quantitative Proteomic Investigation of Spatial-Temporal Interactions of the Outer Tegument Protein pUL46 during HSV-1 Infection

摘要

Quantitative mass spectrometry and isolation of protein complexes provide the opportunity to study dynamic virus-host interactions and elucidate functions of viral proteins. Upon infection, herpes simplex virus type 1 (HSV-1) promotes a dramatic re-arrangement of cellular functions, requiring precisely timed viral gene expression (1). Virion proteins are critical in initiating these expression cascades. The tegument protein pUL48 is essential for inducing immediate early gene expression, but its modulatory proteins pUL46 and pUL47 are less well characterized. pUL46 is thought to be multi-functional, modulating α-trans inducing factor (2), signaling (3), and packaging (4). However, its role during early stages of infection is highly disputed. Here we present the first proteomics study focused on pUL46 interactions, identifying critical viral associations with ICP proteins. Moreover, this represents one of the first few studies utilizing TMT (tandem mass tag, (5)) labeling to quantitatively compare protein complexes. With this technique, we are able to assess dynamic protein-protein interactions throughout different stages of viral infection.