Regulation of Cellular Metabolism by High-Risk Human Papillomaviruses

Abstract

The alteration of glucose metabolism is one of the first biochemical characteristics associated with cancer cells since most of these cells increase glucose consumption and glycolytic rates even in the presence of oxygen, which has been called “aerobic glycolysis” or the Warburg effect. Human papillomavirus (HPV) is associated with approximately 5% of all human cancers worldwide, principally to cervical cancer. E6 and E7 are the main viral oncoproteins which are required to preserve the malignant phenotype. These viral proteins regulate the cell cycle through their interaction with tumor suppressor proteins p53 and pRB, respectively. Together with the viral proteins E5 and E2, E6 and E7 can favor the Warburg effect and contribute to radio- and chemoresistance through the increase in the activity of glycolytic enzymes, as well as the inhibition of the Krebs cycle and the respiratory chain. These processes lead to a fast production of ATP obtained by Warburg, which could help satisfy the high energy demands of cancer cells during proliferation. In this way HPV proteins could promote cancer hallmarks. However, it is also possible that during an early HPV infection, the Warburg effect could help in the achievement of an efficient viral replication.

Differential effect of GLUT1 overexpression on survival and tumor immune microenvironment of human papilloma virus type 16-positive and -negative cervical cancer

“…HPV infection could promote certain cancer hallmarks including immune evasion and epithelial-mesenchymal transition, increasing the activity of glycolytic enzymes 8,9 . Altered tumor metabolic status has been recognized as an important contributing factor to chemo- or radio-resistance.…”

Cervicovaginal Microbiome and Urine Metabolome Paired Analysis Reveals Niche Partitioning of the Microbiota in Patients with Human Papilloma Virus Infections

“…We suggest that the predicted effect produced by Megasphaera could be associated with the change of pyruvate carbon flux towards the release of lactate, rather than conversion to acetyl-CoA. In this case, acetyl-CoA could be further metabolized to CoA and acetate and eventually lead to the malignant transformation of the cervical cells [39].…”

“…Nevertheless, acylphosphatase is known to participate in glycolysis and pyrimidine biosynthesis [38]. Moreover, it is known that the main HPV oncoproteins associated with cervical cancer can favor an increase in the activity of glycolytic enzymes [39]. Thus, the activity of acylphosphatase associated with changes in bacterial composition, including Lactobacillus sp.…”

REBACIN® as a noninvasive clinical intervention for high‐risk human papillomavirus persistent infection

“…In recent decades, HPV studies on therapeutic strategies have proposed several options, including the role of HPV E6 and E7 oncogenes. Considering that the progression to cervical malignancy requires the overexpression of E6 and E7 genes of integrated HPV genome, we further investigated whether this antiviral biologic inhibits the expression of E6 and E7 viral genes. Seventy‐two hours after the application of different concentration of REBACIN® to TC‐1 and Hela cells stably expression of HPV E6/E7, the transcription level of HPV E6/E7 mRNA was examined via RT‐PCR.…”