Metabolic reprogramming during hepatitis B disease progression offers novel diagnostic and therapeutic opportunities

Abstract

Metabolic remodeling occurs in immune cells during an infection. Host cells must upregulate energy production for growth, proliferation, and effector functions to limit the damage imposed by pathogens. One example, the hepatitis B virus, induces hepatic injury in human hepatocytes through dysregulation of aerobic glycolysis and lipid metabolism. Increased glycolytic metabolism mediated by elevated expression of Glut1, glucose influx, and lactate secretion is associated with this Warburg phenotype, a classic metabolic signature also observed in cancer cells. This article brings into focus the tight interaction between HBV infection and metabolic dysfunction and how these processes facilitate the progression of end-stage liver diseases, such as hepatocellular carcinoma. We also provide evidence and models by which other viruses such as HIV and Zika disrupt their host metabolic machinery. The emergence of the immunometabolism field provides novel opportunities to take advantage of intermediary metabolites and key metabolic pathways for diagnostic and therapeutic purposes.

Tissue-resident NK cells differ in their expression profile of the nutrient transporters Glut1, CD98 and CD71

“…Immune cell metabolism is a critical determinant of the function of tissue-resident immune cells, as nutrient availability in tissues can largely vary depending on the specific tissue characteristics and other factors influencing local nutrient availability, such as viral infections [ 23 , 24 , 47 ] and malignancies [ 22 , 48 , 49 ]. Infections and malignancies affect the nutritional microenvironment by changing nutrient supply to tissues, resulting from fibrosis or modulated vascularization [ 50 , 51 ], or by consuming nutrients themselves [ 48 ].…”

“…Many tumor cells possess the ability to significantly increase their glucose uptake, thus decreasing glucose availability for immune cells in their surroundings as a mechanism of immune evasion [ 22 ]. Similarly, certain viruses such as hepatitis B and C virus can modulate the uptake of glucose into infected cells, which also affects the nutritional microenvironment [ 23 , 24 ]. It still remains unknown how tissue-resident NK cells adjust to these changes in available nutrients to fulfill their functional requirements.…”

Chronic hepatitis B virus infection and risk of dyslipidaemia: A cohort study

“…HBV infection in hepatocytes induces hepatic injury through dysregulation of glucose and lipid metabolism, emphasizing the role of metabolic reprogramming during the progression of hepatitis B disease . ApoB in the liver is an important glycoprotein for transportation of very low‐density lipoproteins and low‐density lipoproteins.…”

Potential Therapies for Infectious Diseases Based on Targeting Immune Evasion Mechanisms That Pathogens Have in Common With Cancer Cells

“…To optimize their environment for infection, viruses can alter many host cellular metabolic pathways; in particular, cells infected by actively replicating viruses exhibit cancer phenotypes such as aerobic glycolysis, upregulated glutaminolysis and fatty acid synthesis (Sanchez and Lagunoff, 2015). Viruses such as HBV, HIV, and Zika have been shown to dysregulate glycolysis by increasing GLUT1 expression, glucose influx and lactic acid production in their host cells (Masson et al, 2017). Moreover, an acidified microenvironment resulting from increased lactic acid secretion may contribute to virus-induced pathogenesis, as enveloped viruses' fusion to host cell membrane was observed to be more effective at a low pH (Desai et al, 2017).…”