title: The processivity factor complex of feline herpes virus-1 is a new drug target.
abstract: Feline herpes virus-1 (FHV-1) is ubiquitous in the cat population and is a major cause of blindness for which antiviral drugs, including acyclovir, are not completely effective. Recurrent infections, due to reactivation of latent FHV-1 residing in the trigeminal ganglia, can lead to epithelial keratitis and stromal keratitis and eventually loss of sight. This has prompted the medical need for an antiviral drug that will specifically inhibit FHV-1 infection. A new antiviral target is the DNA polymerase and its associated processivity factor, which forms a complex that is essential for extended DNA strand synthesis. In this study we have cloned and expressed the FHV-1 DNA polymerase (f-UL30) and processivity factor (f-UL42) and demonstrated that both proteins are required to completely synthesize the 7249 nucleotide full-length DNA from the M13 primed-DNA template in vitro. Significantly, a known inhibitor of human herpes simplex virus-1 (HSV-1) processivity complex was shown to inhibit FHV-1 processive DNA synthesis in vitro and block infection of cells. This validates using f-UL42/f-UL30 as a new antiviral drug target to treat feline ocular herpes infection.
authors.affiliation: Department of Microbiology, Penn Dental Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Zhukovskaya
authors.affiliation: Department of Microbiology, Penn Dental Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Hancheng
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Microbiology, Penn Dental Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Yih Ling
authors.initials: YL
authors.lastname: Saw
authors.affiliation: Department of Microbiology, Penn Dental Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Manunya
authors.initials: M
authors.lastname: Nuth
authors.affiliation: Department of Microbiology, Penn Dental Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Abramson Cancer Center, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: ricciard@upenn.edu.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Ricciardi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002415:Cats; D002460:Cell Line; D003001:Cloning, Molecular; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*; D013830:Thiadiazoles / Q000494:pharmacology*; D018140:Varicellovirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; C000602270:N-(2,1,3-benzothiadiazol-4-yl)-5-bromo-2-((4-chlorophenyl)sulfonylamino)benzamide; D013449:Sulfonamides; D013830:Thiadiazoles; D014764:Viral Proteins; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; C043417:DNA polymerase, Simplexvirus
keywords: Antiviral drug target; DNA polymerase; Feline herpes virus; Ocular herpes keratitis; Processive DNA synthesis; Processivity factor