title: Marek's disease: Genetic regulation of gallid herpesvirus 2 infection and latency.
abstract: Gallid herpesvirus-2 (GaHV-2) is an oncogenic α-herpesvirus that causes Marek's disease (MD), a T cell lymphosarcoma (lymphoma) of domestic fowl (chickens). The GaHV-2 genome integrates by homologous recombination into the host genome and, by modulating expression of viral and cellular genes, induces transformation of latently infected cells. MD is a unique model of viral oncogenesis. Mechanisms implicated in the regulation of viral and cellular genes during GaHV-2 infection operate at transcriptional, post-transcriptional and post-translational levels, with involvement of viral and cellular transcription factors, along with epigenetic modifications, alternative splicing, microRNAs and post-translational modifications of viral proteins. Meq, the major oncogenic protein of GaHV-2, is a viral transcription factor that modulates expression of viral genes, for example by binding to the viral bidirectional promoter of the pp38-pp24/1.8 kb mRNA, and also modulates expression of cellular genes, such as Bcl-2 and matrix metalloproteinase 3. GaHV-2 expresses viral telomerase RNA subunit (vTR), which forms a complex with the cellular telomerase reverse transcriptase (TERT), thus contributing to tumorigenesis, while vTR independent of telomerase activity is implicated in metastasis. Expression of a viral interleukin 8 homologue may contribute to lymphomagenesis. Inhibition of expression of the pro-apoptotic factors JARID2 and SMAD2 by viral microRNAs may promote the survival and proliferation of GaHV-2 latently infected cells, thus enhancing tumorigenesis, while inhibition of interleukin 18 by viral microRNAs may be involved in evasion of immune surveillance. Viral envelope glycoproteins derived from glycoprotein B (gp60 and gp49), as well as glycoprotein C, may also play a role in immune evasion.
authors.affiliation: Veterinary Integrated Research Unit, Faculty of Sciences, Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), 5000 Namur, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gennart
authors.affiliation: Veterinary Integrated Research Unit, Faculty of Sciences, Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), 5000 Namur, Belgium.
authors.forename: Damien
authors.initials: D
authors.lastname: Coupeau
authors.affiliation: Veterinary Integrated Research Unit, Faculty of Sciences, Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), 5000 Namur, Belgium.
authors.forename: Srdan
authors.initials: S
authors.lastname: Pejaković
authors.affiliation: Transcription, Lymphome Viro-Induit, University François Rabelais, UFR Sciences et Techniques, Parc de Grandmont, F-37200 Tours, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Laurent
authors.affiliation: Transcription, Lymphome Viro-Induit, University François Rabelais, UFR Sciences et Techniques, Parc de Grandmont, F-37200 Tours, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Rasschaert
authors.affiliation: Veterinary Integrated Research Unit, Faculty of Sciences, Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), 5000 Namur, Belgium. Electronic address: benoit.muylkens@unamur.be.
authors.forename: Benoit
authors.initials: B
authors.lastname: Muylkens
mesh_terms: D000818:Animals; D002645:Chickens; D015967:Gene Expression Regulation, Viral; D008381:Herpesvirus 2, Gallid / Q000235:genetics*; D006801:Humans; D008380:Marek Disease / Q000821:virology*; D011201:Poultry Diseases / Q000821:virology*; D017735:Virus Latency
keywords: Epigenetics; Gallid herpesvirus-2; Gene regulation; Marek's disease; Virus induced lymphoma