The Pleiotropic Function of Human Sirtuins as Modulators of Metabolic Pathways and Viral Infections

Abstract

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent histone deacetylases that incorporate complex functions in the mechanisms of cell physiology. Mammals have seven distinct members of the SIRT family (SIRT1-7), which play an important role in a well-maintained network of metabolic pathways that control and adapt the cell to the environment, energy availability and cellular stress. Until recently, very few studies investigated the role of SIRTs in modulating viral infection and progeny. Recent studies have demonstrated that SIRT1 and SIRT2 are promising antiviral targets because of their specific connection to numerous metabolic and regulatory processes affected during infection. In the present review, we summarize some of the recent progress in SIRTs biochemistry and their emerging function as antiviral targets. We also discuss the potential of natural polyphenol-based SIRT modulators to control their functional roles in several diseases including viral infections.

Sirtuins as Potential Therapeutic Targets for Hepatitis B Virus Infection

“…The SIRT protein was first discovered in Saccharomyces cerevisiae as a silent information regulator 2 (SIR2) that contributes to extension of life span under different types of stress ( 17 – 19 ). To date, a total of seven mammalian SIRT proteins have been identified.…”

“…Additionally, all SIRTs are members of class III histone deacetylases. In addition to their constitutive deacetylase activity, some SIRTs have alternative enzymatic activities, including ADP ribosyltransferase (SIRT4 and SIRT6), demalonylase (SIRT5), desuccinylase (SIRT5 and SIRT7), and demyristoylase (SIRT6) ( 18 , 19 ). Given their diverse localizations and enzymatic activities, SIRTs are known to play a significant role in a wide range of biological functions.…”

“…Given their diverse localizations and enzymatic activities, SIRTs are known to play a significant role in a wide range of biological functions. Owing to their ability to target various cellular substrates, SIRTs are crucial for numerous biological processes, including DNA repair, proliferation, mitochondrial energy homeostasis, and metabolism ( 17 , 19 ). In particular, increasing evidence shows that SIRTs are implicated in the persistence and pathogenesis of viral infections ( 20 ) caused by human immunodeficiency virus, influenza A virus, herpes simplex virus 1, and human papillomavirus ( 18 , 19 ).…”

“…Owing to their ability to target various cellular substrates, SIRTs are crucial for numerous biological processes, including DNA repair, proliferation, mitochondrial energy homeostasis, and metabolism ( 17 , 19 ). In particular, increasing evidence shows that SIRTs are implicated in the persistence and pathogenesis of viral infections ( 20 ) caused by human immunodeficiency virus, influenza A virus, herpes simplex virus 1, and human papillomavirus ( 18 , 19 ). Considering the potential importance of SIRTs in viral infections, an improved understanding of the interaction between SIRTs and viruses may help researchers to develop alternative novel antiviral therapeutic agents.…”

Sirtuins as Interesting Players in the Course of HIV Infection and Comorbidities

“…Given the diverse localizations and activities described above, sirtuins are core regulators of metabolism and transcription. They have the ability to control numerous cellular pathways required throughout the viral life cycle, but the exact role of sirtuins in viral infections has not yet been fully understood [11].…”