Defective transport of herpes simplex virus glycoprotein in interferon-treated cells: role of intracellular pH.
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.
Maheshwari
R K
RK
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Sidhu
G S
GS
Singh
A K
AK
Sivaram
S S
SS
Kinchington
P R
PR
Hay
J
J
Friedman
R M
RM
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000502:physiology; D006056:Golgi Apparatus; D022283:Herpesvirus Vaccines; D006863:Hydrogen-Ion Concentration; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D018139:Simplexvirus; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000378:metabolism*; D014765:Viral Vaccines / Q000378:metabolism*
D022283:Herpesvirus Vaccines; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C069093:herpes simplex virus-1 glycoprotein D vaccine; D016899:Interferon-beta