Resistance of herpes simplex virus type 2 to neomycin maps to the N-terminal portion of glycoprotein C.
Entry of herpes simplex virus (HSV) into cells is believed to be mediated by specific binding of envelope proteins to a cellular receptor. Neomycin specifically blocks this initial step in infection by HSV-1 but not HSV-2. Resistance of HSV-2 to this compound maps to a region of the genome encoding glycoprotein C (gC-2). We have studied the function of gC-2 in the initial interaction of the virus with the host cell, using HSV-2 mutants deleted for gC-2 and gC-2-rescued recombinants. Resistance to neomycin was directly linked to the presence of gC-2 within the viral genome. In addition, deletion of the gC-2 gene caused a marked delay in adsorption to cells relative to the wild-type virus. HSV-1 recombinants containing chimeric gC genes composed of HSV-1 and HSV-2 sequences were used to localize neomycin resistance within the N-terminal 223 amino acids of gC-2. This region of the glycoprotein comprises an important domain responsible for binding of HSV-2 to cell receptors in the presence of neomycin. A gC-2-negative mutant is still infectious, indicating that HSV-2 also has an alternative pathway of adsorption.
Department of Microbiology and Immunology, Gade Institute, University of Bergen, Norway.
A M
AM
Oyan
K E
KE
Dolter
N
N
Langeland
W F
WF
Goins
J C
JC
Glorioso
L
L
Haarr
C S
CS
Crumpacker
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002999:Clone Cells; D006224:Cricetinae; D004274:DNA, Recombinant; D004279:DNA, Viral / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D017353:Gene Deletion; D008969:Molecular Sequence Data; D009154:Mutation; D009355:Neomycin / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D011995:Recombination, Genetic; D018139:Simplexvirus / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000032:analysis; D014779:Virus Replication
D004274:DNA, Recombinant; D004279:DNA, Viral; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C048232:glycoprotein C, herpes simplex virus type 2; D009355:Neomycin