Defective transport of herpes simplex virus glycoprotein in interferon-treated cells: role of intracellular pH.

Abstract

We have investigated the mechanism(s) of interferon (IFN)-induced inhibition of assembly steps of herpes simplex virus (HSV-1) in mouse LB cells. Data showed that physiological doses of mouse IFN-beta (10-100 IU/ml) significantly inhibited the infectivity (5- to 100-fold) of HSV-1; however, viral protein synthesis was marginally inhibited (2- to 5-fold). Immunofluorescence studies showed that most of the HSV-1gD glycoprotein accumulated intracellularly in IFN-treated LB and LMtk- cells transfected with gD cDNA, as compared to untreated controls, where most of the gD was localized on the plasma membrane. Double-immunofluorescence studies demonstrated that rhodamine-labeled wheat germ agglutinin (WGA) was co-localized with gD protein, suggesting the block was in the transport from the trans-Golgi to the plasma membrane. IFN treatment of LB and LMtk- cells raised the intracellular pH as measured by DAMP distribution and SNARF-1 using laser spectroscopy; this could play an important role in the inhibition of transport of HSV-1gD.