title: Identification of B cells as a major site for cyprinid herpesvirus 3 latency.
abstract: Cyprinid herpesvirus 3 (CyHV-3), commonly known as koi herpesvirus (KHV), is a member of the Alloherpesviridae, and is a recently discovered emerging herpesvirus that is highly pathogenic for koi and common carp. Our previous study demonstrated that CyHV-3 becomes latent in peripheral white blood cells (WBC). In this study, CyHV-3 latency was further investigated in IgM(+) WBC. The presence of the CyHV-3 genome in IgM(+) WBC was about 20-fold greater than in IgM(-) WBC. To determine whether CyHV-3 expressed genes during latency, transcription from all eight open reading frames (ORFs) in the terminal repeat was investigated in IgM(+) WBC from koi with latent CyHV-3 infection. Only a spliced ORF6 transcript was found to be abundantly expressed in IgM(+) WBC from CyHV-3 latently infected koi. The spliced ORF6 transcript was also detected in vitro during productive infection as early as 1 day postinfection. The ORF6 transcript from in vitro infection begins at -127 bp upstream of the ATG codon and ends +188 bp downstream of the stop codon, +20 bp downstream of the polyadenylation signal. The hypothetical protein of ORF6 contains a consensus sequence with homology to a conserved domain of EBNA-3B and ICP4 from Epstein-Barr virus and herpes simplex virus 1, respectively, both members of the Herpesviridae. This is the first report of latent CyHV-3 in B cells and identification of gene transcription during latency for a member of the Alloherpesviridae.
  
  
  OBJECTIVE
  This is the first demonstration that a member of the Alloherpesviridae, cyprinid herpesvirus 3 (CyHV-3), establishes a latent infection in the B cells of its host, Cyprinus carpio. In addition, this is the first report of identification of gene transcription during latency for a member of Herpesvirales outside Herpesviridae. This is also the first report that the hypothetical protein of latent transcript of CyHV-3 contains a consensus sequence with homology to a conserved domain of EBNA-3B from Epstein-Barr virus and ICP4 from herpes simplex virus 1, which are genes important for latency. These strongly suggest that latency is evolutionally conserved across vertebrates.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA Department of Microbiology, College of Science, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Aimee N
authors.initials: AN
authors.lastname: Reed
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Satoko
authors.initials: S
authors.lastname: Izume
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Dolan
authors.affiliation: Research Division, Clear Springs Foods, Inc., Buhl, Idaho, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: LaPatra
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA Department of Microbiology, College of Science, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kent
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA Department of Microbiology, College of Science, Oregon State University, Corvallis, Oregon, USA ling.jin@oregonstate.edu.
authors.forename: Ling
authors.initials: L
authors.lastname: Jin
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000821:virology*; D001483:Base Sequence; D002347:Carps / Q000821:virology*; D002460:Cell Line; D005393:Fish Diseases / Q000821:virology; D006564:Herpesviridae / Q000235:genetics* / Q000472:pathogenicity*; D006566:Herpesviridae Infections / Q000821:virology*; D007075:Immunoglobulin M / Q000235:genetics; D007962:Leukocytes / Q000821:virology; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000235:genetics; D017735:Virus Latency / Q000235:genetics*
chemical_list: D007075:Immunoglobulin M