A truncation mutation of the neurovirulence ICP22 protein produced by a recombinant HSV-1 generated by bacterial artificial chromosome technology targets infected cell nuclei

• Published in: Journal of neurovirology Vol. 17; no. 6; pp. 559 - 569
• Main Authors: Bowles, Robert N., Blaho, John A.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2011; Springer
• Subjects: Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cell Nucleus - genetics; Cell Nucleus - virology; Cercopithecus aethiops; Chromosomes, Artificial, Bacterial; Gene Expression Regulation, Viral; Herpes Simplex - virology; Herpes simplex virus 1; Herpesvirus 1, Human - genetics; Herpesvirus 1, Human - pathogenicity; Human viral diseases; Humans; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Immunology; Infectious Diseases; Medical sciences; Mice; Mutation; Neurology; Neurosciences; Primates; Rabbits; RNA, Messenger - genetics; RNA, Viral - genetics; Transcription, Genetic; Vero Cells; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral diseases of the nervous system; Virology; Virulence Factors - genetics; Virulence Factors - metabolism; Virus Replication - genetics; Bacterial artificial chromosome; ICP22; Neurovirulence; Herpes simplex virus; Nervous system diseases; Herpesviridae; Alphaherpesvirinae; Chromosome; Infection; Virus; Technology; Viral disease; Bacteriosis; Human herpesvirus 1; Herpesvirus hominis; Mutation; Recombinant protein
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1007/s13365-011-0064-z

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.