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Marek’s Disease Virus



          Blanca M. Lupiani , Yifei Liao , Di Jin , Yoshihiro Izumiya  and Sanjay M. Reddy *          12
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          1 College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
          2 School of Medicine, University of California Davis, Sacramento, CA, USA.
          *Correspondence: sreddy@cvm.tamu.edu
          https://doi.org/10.21775/9781912530106.12







          Abstract                                              the disease as ‘fowl paralysis’ or ‘range paralysis’ since the disease
          Marek’s disease virus (MDV) is a highly oncogenic alphaherpes-  primarily affected peripheral nerves leading to paralysis.
          virus that infects chickens, causing enormous economic losses   Later studies showed that in addition to lesions in the nerves,
          to the poultry industry. MDV belongs to the genus Mardivirus   tumours were observed in various lymphoid organs (Pap-
          and is classified into three serotypes. Only viruses belonging to   penheimer, 1926, 1929). It was difficult to distinguish visceral
          serotype 1 cause disease in chickens. In susceptible chickens,   lymphomas caused by ‘range paralysis’ from neoplastic condi-
          T-lymphocytes undergo neoplastic transformation. The manifes-  tions of the haematopoietic system in chickens. These distinct
          tation of the disease depends on the distribution of the neoplastic   diseases were initially described as Avian Leukosis Complex, but
          lesions. Typically, the disease is manifested by visible lymphomas   later it was concluded that they were distinct diseases caused by
          in various visceral organs and paralysis. Highly pathogenic MDV   different viral aetiological agents.
          also causes neurological disease and immunosuppression. MDV
          is controlled by vaccination using live attenuated vaccines, but
          vaccinated chickens do not provide sterilizing immunity and   Infectious agent
          cannot block virus transmission of field strains. Vaccination is
          generally believed to have contributed to increase in virulence of   Classification
          the filed strains leading to vaccine breaks. Among several genes   MD is a common, highly contagious, lymphoproliferative disease
          encoded by MDV, meq, which encodes a bZIP protein, appears   of  chickens  characterized  by  T-cell  tumours,  immunosuppres-
          to play a critical role in the transformation of lymphocytes. With   sion, partial or complete paralysis of legs and wings, skin leukosis,
          the availability of genome manipulation tools and a natural host   depression, and death (Marek, 1907; Pappenheimer et al., 1929;
          system, MDV provides a relevant model to explore the molecular   Calnek, 2001). The causative agent of MD is Marek’s disease virus
          mechanisms of viral oncogenesis. In this chapter, we summarize   (MDV serotype 1) or Gallid herpesvirus 2 (GaHV-2), and along
          the current knowledge of MDV molecular biology, pathogenesis   with two other non-oncogenic poultry viruses, Gallid herpesvirus
          and control, as well as the role of individual viral genes in replica-  3 (GaHV-3 or MDV serotype 2) and  Meleagrid herpesvirus 1
          tion and transformation.                              [MeHV-1, MDV serotype 3 or turkey herpesvirus (HVT)], are
                                                                classified in the genus Mardivirus of the subfamily Alphaherpes-
                                                                virinae (Davison et al., 2009). MDV-1 includes oncogenic viruses
          Introduction and history                              of  variable  virulence,  MDV-2  includes  non-oncogenic  viruses
          Marek’s disease (MD) is a lymphoproliferative disease of chick-  from chickens, and MDV-3 includes non-oncogenic viruses from
          ens caused by a herpesvirus. MD was first described by Dr Joseph   turkeys (Table 12.1). The MDV-1 pathogenic strains vary greatly
          Marek, a clinical pathologist at the Royal Hungarian Veterinary   in their pathogenic and oncogenic potential and were originally
          School in Budapest, in 1907. In his seminal report entitled ‘Mul-  classified as either classical or acute forms of MD (Biggs et al.,
          tiple Nervenentzündung (polyneuritis) bei Hühnern (chickens)’   1965). The classical form referred to less pathogenic strains with
          (Marek, 1907), he described the disease in four adult cockerels   paralytic manifestation of the disease and the acute form referred
          that were affected by paralysis of wings and legs. The affected   to strains that caused lymphomas in visceral organs. With the
          chickens showed thickening of the sacral plexus due to infiltration   isolation of viruses with greater virulence than acute viruses this
          of the mononuclear cells. He described the disease as a neurologi-  classification became inadequate. An alternate nomenclature
          cal disease of chickens due to polyneuritis of the affected nerves.   was proposed in which the classical strains were considered mild
          A similar condition was reported in the USA and in the Nether-  MDV (mMDV) and acute strains were classified based on their
          lands in the 1920s. These early descriptions led to the naming of   ability to cause increasing disease in chickens vaccinated with
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