Herpes simplex virus type 1 glycoprotein C is necessary for efficient infection of chondroitin sulfate-expressing gro2C cells.
The role of glycoprotein C (gC) for binding of herpes simplex virus type 1 (HSV-1) to cell surface chondroitin sulfate (CS) and the consequences of this interaction for virus attachment and infectivity were studied. To this end, a panel of HSV-1 gC mutants, including a gC-negative (gC(-)) variant, and mouse fibroblasts expressing either cell surface CS or heparan sulfate (HS) were used. Comparing gC-positive (gC(+)) and gC(-) viruses in terms of their attachment to and infection of CS-expressing cells indicated that gC was essential for both functions. Furthermore, purified gC bound efficiently to isolated CS chains. However, hypertonic NaCl disrupted this interaction more easily as compared to the binding of gC to HS. Also, native and selectively desulfated heparins were approximately 10 times more efficient at inhibiting gC binding to CS-expressing cells than binding to HS-expressing cells. Experiments with the HSV-1 gC mutants revealed that specific, positively charged and hydrophobic amino acids within the N-terminal part of the protein were responsible for efficient binding as well as infectivity in both CS- and HS-expressing cells. When the infectivity of the gC mutants in the two cell types was compared, it appeared that more residues contributed to the infection of CS-expressing cells than to infection of HS-expressing cells. Taken together, analysis of gC function in cell systems with limited expression of glycosaminoglycans revealed that gC could interact with either CS or HS and that these interactions exhibited subtle but definite differences as regards to the involved structural features of gC, ionic strength dependency as well as sensitivity to specifically desulfated heparin compounds.
Mårdberg
Kristina
K
Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, S-413 46 Göteborg, Sweden1.
Trybala
Edward
E
Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, S-413 46 Göteborg, Sweden1.
Tufaro
Frank
F
Department of Microbiology and Immunology, University of British Columbia, 300-6174 University Boulevard, Vancouver, BC, CanadaV6T 1Z32.
Bergström
Tomas
T
Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, S-413 46 Göteborg, Sweden1.
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D002809:Chondroitin Sulfates / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000235:genetics / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D051379:Mice; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
D002809:Chondroitin Sulfates; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1