Abstract
Herpes simplex virus type 1 (HSV-1) mutants were selected by passage of HSV-1 (KOS) in HEp-2 cells such that binding and penetration occurred in the presence of heparin. Analysis of selected uncloned virus pools revealed that approximately 95% of virus formed syncytia and greater than 58% were gC-negative. Plaque-purified gC-negative syncytial mutants were more resistant than HSV-1 (KOS) to heparin inhibition, as was an engineered nonsyncytial recombinant deleted for gC, delta gC6. Thus, absence of gC was sufficient to explain the enrichment for gC-negative mutants. The syncytial phenotype of most mutants mapped to a mutation in gK. Transfer of this mutation to HSV-1 (KOS) resulted in a recombinant that induced fusion of Vero cells but not HEp-2 cells and was more sensitive to heparin inhibition of entry, revealing a previously undescribed phenotype of mutations in gK. Engineered gC-negative virus containing the gK syncytial mutation induced fusion of both cell lines and was as resistant to heparin inhibition as was delta gC6. Because deletion of gC reduces infectivity of HSV-1 in the absence of heparin, mutations in gC combined with the syncytial mutation could have provided a selective advantage. Thus, absence of gC reduced h...Continue Reading
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