TitleIdentification of B cells as a major site for cyprinid herpesvirus 3 latency.
Publication TypeJournal Article
Year of Publication2014
AuthorsReed, AN, Izume, S, Dolan, BP, Lapatra, S, Kent, ML, Dong, J, Jin, L
JournalJ Virol
Volume88
Issue16
Pagination9297-309
Date Published2014 Aug
ISSN1098-5514
KeywordsAnimals, B-Lymphocytes, Base Sequence, Carps, Cell Line, Fish Diseases, Herpesviridae, Herpesviridae Infections, Immunoglobulin M, Leukocytes, Molecular Sequence Data, Open Reading Frames, Sequence Alignment, Transcription, Genetic, Virus Latency
Abstract

UNLABELLED: 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.

IMPORTANCE: 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.

DOI10.1128/JVI.00990-14
Alternate JournalJ Virol
PubMed ID24899202
PubMed Central IDPMC4136273
Grant ListT32 OD011020 / OD / NIH HHS / United States
T32 RR023917 / RR / NCRR NIH HHS / United States
RR023917 / RR / NCRR NIH HHS / United States
T32OD011020 / OD / NIH HHS / United States