Metabolic Control by DNA Tumor Virus-Encoded Proteins

Abstract

Viruses co-opt a multitude of host cell metabolic processes in order to meet the energy and substrate requirements for successful viral replication. However, due to their limited coding capacity, viruses must enact most, if not all, of these metabolic changes by influencing the function of available host cell regulatory proteins. Typically, certain viral proteins, some of which can function as viral oncoproteins, interact with these cellular regulatory proteins directly in order to effect changes in downstream metabolic pathways. This review highlights recent research into how four different DNA tumor viruses, namely human adenovirus, human papillomavirus, Epstein–Barr virus and Kaposi’s associated-sarcoma herpesvirus, can influence host cell metabolism through their interactions with either MYC, p53 or the pRb/E2F complex. Interestingly, some of these host cell regulators can be activated or inhibited by the same virus, depending on which viral oncoprotein is interacting with the regulatory protein. This review highlights how MYC, p53 and pRb/E2F regulate host cell metabolism, followed by an outline of how each of these DNA tumor viruses control their activities. Understanding how DNA tumor viruses regulate metabolism through viral oncoproteins could assist in the discovery or repurposing of metabolic inhibitors for antiviral therapy or treatment of virus-dependent cancers.

The EBV Gastric Cancer Resource (EBV-GCR): A Suite of Tools for Investigating EBV-Associated Human Gastric Carcinogenesis

“…EBV uses a variety of immune evasion strategies to establish lifelong latent infections [5]. Furthermore, EBV expresses several oncogenic proteins and microRNAs (miRNAs) [6,7] that are mechanistically associated with multiple types of cancers, including Burkitt's and other lymphomas, nasopharyngeal carcinomas, and EBV-associated gastric adenocarcinomas (EBVaGCs) [8]. Overall, EBV infections account for 1.5% of all human cancer cases worldwide [9].…”

GLUT1, LDHA, and MCT4 Expression Is Deregulated in Cervical Cancer and Precursor Lesions

“…The E6 and E7 oncoproteins of both viruses show the capacity to interact with MYC, which regulates glycolysis through genes such as LDHA and GLUT1, and with P53, which negatively regulates glycolysis through GLUT1 and GLUT4. 21 A recent study analyzed the expression of GLUT1 with HPV-16 positivity but did not find significant differences between a high or low expression of GLUT1 in the presence or absence of this viral type. 22 Therefore, we analyzed GLUT1, LDHA, and MCT4 metabolic proteins in CIN and ICC in the presence of HR-HPV, because not only HPV-16 but also the other oncogenic HPVs frequent in our population could be participating in this event.…”

New Look of EBV LMP1 Signaling Landscape

“…Cancer metabolism is an old theme, but it has attracted intensive attention in recent years with deeper mechanistic insights. Not only ER-mediated UPR, which can be induced by high levels of LMP1, is involved in regulating lipid and glucose metabolism [127,128], but also LMP1 regulates mitochondrial NAD (NAD+ and NADH) and NADP (NADP+ and NADPH) energy metabolism as well as other metabolism pathways [129][130][131].…”

“…LMP1 also promotes glycolysis by constitutively activating the FGF2-FGFR1 signaling pathway, and by upregulating the glycolysis-related hexokinase 2 (HK2) and IDH2, and HIF1α-mediated PDK1 and PKM2, and by repressing the expression of HOX genes [131]. Furthermore, in EBV lymphomas, LMP1 promotes glucose metabolism through stabilization of c-Myc, promoting c-Myc activity, and also through upregulation of c-Myc expression via STAT3 [129].…”