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Authors: Tailor, Prafullakumar
Kumari, Puja
Saha, Irene
Narayanan, Athira
Narayanan, Sathish
Takaoka, Akinori
Kumar, Nachimuthu Senthil
Kumar, Himanshu
Title: Essential role of HCMV deubiquitinase in promoting oncogenesis by targeting anti-viral innate immune signaling pathways
Publisher: Springer Nature
Publication Date: Oct-2017
Abstract: Cancer is a multifactorial disease and virus-mediated carcinogenesis is one of the crucial factors, which is poorly understood. Human cytomegalovirus (HCMV) is a herpesvirus and its components have been evidenced to be associated with cancer of different tissue origin. However, its role in cancer remains unknown. Here, we identified a conserved herpesviral tegument protein known as pUL48 of HCMV, encoding deubiquitinase enzyme, as having a key role in carcinogenesis. We show using deubiquitinase sufficient- and deficient-HCMV that HCMV deubiquitinase is a key in inducing enhanced cellular metabolic activity through upregulation of several anti-apoptotic genes and downregulation of several pro-apoptotic genes expression. Furthermore, HCMV deubiquitinase acquires pro-tumor functions by inhibiting PRR-mediated type I interferon via deubiquitination of TRAF6, TRAF3, IRAK1, IRF7 and STING. Taken together, our results suggest that HCMV infection may promote oncogenesis by inhibiting innate immunity of the host.
Issue No: 10
Appears in Collections:Innate Immunity, Publications

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