title: A truncation mutation of the neurovirulence ICP22 protein produced by a recombinant HSV-1 generated by bacterial artificial chromosome technology targets infected cell nuclei.
abstract: The major regulatory protein ICP22 is unique among the immediate early proteins of herpes simplex virus. Viruses deleted for ICP22 replicate well in actively dividing cells, but not in quiescent cells or certain rodent lines. Accordingly, ICP22 represents an understudied herpes simplex virus (HSV) neurovirulence marker which is absolutely essential for viral neurogrowth. We utilized the bacterial artificial chromosome methodology to create a novel ICP22 truncation mutant, termed HSV-1(BACX). The integrity of HSV-1(BACX) was confirmed by detailed polymerase chain reaction analyses and immunoblotting using anti-ICP22 antibody. HSV-1(BACX) showed a reduced replication capacity in rabbit skin cells, consistent with previous studies using ICP22-null viruses. Importantly, HSV-1(BACX) localized to nuclei of infected primate Vero cells in a manner similar to wild-type ICP22. Thus, HSV-1(BACX) will serve as a useful tool to decipher the unusual biological properties and functions of the ICP22 protein.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Bowles
authors.forename: John A
authors.initials: JA
authors.lastname: Blaho
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000821:virology; D002522:Chlorocebus aethiops; D022202:Chromosomes, Artificial, Bacterial; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D011817:Rabbits; D014158:Transcription, Genetic; D014709:Vero Cells; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
chemical_list: C057294:ICP22 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D037521:Virulence Factors