Molecular basis for resistance of herpes simplex virus type 1 mutants to the sulfated oligosaccharide inhibitor PI-88.
Herpes simplex virus type 1 variants selected by virus propagation in cultured cells in the presence of the sulfated oligosaccharide PI-88 were analyzed. Many of these variants were substantially resistant to the presence of PI-88 during their initial infection of cells and/or their cell-to-cell spread. Nucleotide sequence analysis revealed that the deletion of amino acids 33-116 of gC but not lack of gC expression provided the virus with selective advantage to infect cells in the presence of PI-88. Purified gC (Delta33-116) was more resistant to PI-88 than unaltered protein in its binding to cells. Alterations that partly contributed to the virus resistance to PI-88 in its cell-to-cell spread activity were amino acid substitutions Q27R in gD and R770W in gB. These results suggest that PI-88 targets several distinct viral glycoproteins during the course of initial virus infection and cell-to-cell spread.
Ekblad
Maria
M
Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, S-413 46, Göteborg, Sweden.
Adamiak
Beata
B
Bergefall
Kicki
K
Nenonen
Hannah
H
Roth
Anette
A
Bergstrom
Tomas
T
Ferro
Vito
V
Trybala
Edward
E
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004279:DNA, Viral; D004352:Drug Resistance, Microbial / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009844:Oligosaccharides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000187:drug effects* / Q000235:genetics
D000596:Amino Acids; D004279:DNA, Viral; D009844:Oligosaccharides; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1; C120158:phosphomannopentaose sulfate