Two Novel Single Amino Acid Syncytial Mutations in the Carboxy Terminus of Glycoprotein B of Herpes Simplex Virus Type 1 Confer a Unique Pathogenic Phenotype

摘要: Abstract We previously reported on a variant of the herpes simplex type 1 (HSV-1) strain 17 syn + , named hep syn, capable forming giant polykaryocytes (syncytia) in tissue culture and which induced striking alteration pathogenesis infection vivo . Following footpad inoculation mice, resulted marked clinicopathologic acute inflammatory response inoculated limb mice died without antecedent paralysis typical wild-type infection. The syncytial pathogenic phenotypes were mapped to cloned 670-base pair Kpn I- Pst I (0.345-0.351 map units) DNA fragment encoding carboxy terminal portion glycoprotein B (gB). In this report, we focus genetics region gB gene that conferred both 57 Five × recombinant viruses, R1-R5, generated marker transfer experiments with fragments containing sequences, produced syn-like disease mice. Sequence analysis revealed single base change when compared sequence, predicting an alanine (GCC codon) valine (GTC amino acid substitution at residue 825 mature protein, plus loss Nco restriction endonuclease site. Southern blot digests vital DNAs showed all recombinants except R4 contained same mutation as syn. phenotype was, however, other recombinants, sequence clone another leucine (CTC histadine (CAC 787 gB. mutant gBs did not effect viral growth viruses had similar vitro replication kinetics wild HSV-1. These data provide direct evidence least two mutations can exist terminus HSV-1 promote formation