Bajwa, Kanika (2020-12). Role of Meq-vIL8 in the Pathogenesis of Marek's Disease Virus. Doctoral Dissertation.
Marek's disease virus (MDV) is a cell-associated and highly oncogenic alphaherpesvirus that infects chickens. MDV genome consists of the unique long (UL) and unique short (US) regions, which are flanked by terminal repeat long (TRL) and short (TRS) and internal repeat long (IRL) and short regions (IRS). In comparison to other herpesviruses, the unique genes found in MDV are primarily found in the repeat long region. They include genes like meq, vIL8, viral telomerase RNA (vTR), RLORF4, RLORF5, MDV encoded microRNA, phosphoprotein 38 (pp38; at the junction of UL and IRL region) genes. Meq is the major oncoprotein of the virus and is involved in T cell transformation in vitro and in vivo. The deletion of both copies of the meq gene showed that it is essential for the transformation of lymphocytes but not required for cytolytic infection in the feather follicular epithelium (FFE) and lymphoid organs in vivo. MDV encoded vIL8 is a CXC chemokine and is a chicken interleukin-8 homolog. vIL8 is expressed in both the lytic and latent infection phases of the virus cycle in vivo, and the deletion of vIL8 severely impairs disease progression and tumor development. Unlike other herpesviruses, extensive splicing activity has also been observed in the repeat regions of the MDV genome. One such splice transcript is between the leucine zipper domain of meq and exons II and III of vIL8, resulting in a meq-vIL8 spliced transcript. The meq-vIL8 encodes a 28kDa nuclear protein, which has been detected in both, a MDV transformed lymphoid cell line, MKT-1, as well as in cells infected with the nonpathogenic MDV vaccine strain CVI988. However, it remains unclear whether the phenotypes observed during the deletion of meq and vIL8 were due to the lack of expression of Meq and vIL8 or due to the disruption of Meq-vIL8 expression. The goal of this research is to delineate the role of the Meq-vIL8 in the pathogenesis of MDV.