title: A varicella-zoster virus mutant impaired for latency in rodents, but not impaired for replication in cell culture.
abstract: While trying to generate a site-directed deletion in the ORF63 latency-associated gene of varicella-zoster virus (VZV) Oka, we constructed a virus with an unexpected rearrangement. The virus has a small deletion in both copies of ORF63 and two copies of a cassette inserted between ORFs 64/65 and 68/69 containing (a) truncated ORF62, (b) ORF63 with a small deletion, and (c) full-length ORF64. The virus was not impaired for growth in human cells, induced higher levels of neutralizing antibodies in guinea pigs, and was impaired for latency in cotton rats compared with parental virus (p=0.0022). Additional mutants containing the same truncation in ORF62, with or without the ORF63 deletion, were less impaired for latency. A VZV Oka mutant, replicating to similar titers and inducing a comparable immune response as parental virus, but impaired for latency, might serve as a safer vaccine and be less likely to reactivate to cause zoster.
authors.affiliation: Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Aruna P N
authors.initials: AP
authors.lastname: Ambagala
authors.forename: Tammy
authors.initials: T
authors.lastname: Krogmann
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.forename: Lesley
authors.initials: L
authors.lastname: Pesnicak
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006168:Guinea Pigs; D006562:Herpes Zoster / Q000821:virology; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D017384:Sequence Deletion; D016205:Sigmodontinae; D014759:Viral Envelope Proteins / Q000235:genetics*; D017735:Virus Latency
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D017874:Immediate-Early Proteins; D014759:Viral Envelope Proteins; C074551:immediate early protein 63, Human herpesvirus 3