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

Jurkowska, Karolina; Szymańska, Beata; Knysz, Brygida; Kuźniarski, Amadeusz; Piwowar, Agnieszka

doi:10.3390/cells10102739

Cited by 11 publications

(7 citation statements)

References 173 publications

(264 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The exact mechanism by which IFN-I interacts with TGF-β to cooperatively activate SMAD2/3 in HepSC is not clearly defined yet but will provide critical insights on how HIV-induced IFN-I contributes to liver fibrosis. SIRT3 signaling has been reported with antifibrotic and antiinflammatory activity ( 59 – 61 ). It is possible that IFN-I and TGF-β may cooperatively reduce SIRT3 signaling, leading to enhancement of HepSC activation and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Type I interferons and TGF-β cooperate to induce liver fibrosis during HIV-1 infection under antiretroviral therapy

Ahodantin¹,

Nio²,

Funaki³

et al. 2022

JCI Insight

View full text Add to dashboard Cite

Liver diseases have become a major comorbidity health concern for people living with HIV-1 (PLWH) treated with combination antiretroviral therapy (cART). To investigate if HIV-1 infection and cART interact to lead to liver diseases, humanized mice reconstituted with progenitor cells from human fetal livers were infected with HIV-1 and treated with cART. We report here that chronic HIV-1 infection with cART induced hepatitis and liver fibrosis in humanized mice, associated with accumulation of M2-like macrophages (M2LMs), elevated TGF-β, and IFN signaling in the liver. Interestingly, IFN-I and TGF-β cooperatively activated human hepatic stellate cells (HepSCs) in vitro. Mechanistically, IFN-I enhanced TGF-β–induced SMAD2/3 activation in HepSCs. Finally, blockade of IFN-I signaling reversed HIV/cART-induced liver diseases in humanized mice. Consistent with the findings in humanized mice with HIV-1 and cART, we detected elevated markers of liver injury, M2LMs, and of IFN signaling in blood specimens from PLWH compared with those of healthy individuals. These findings identify the IFN-I/M2LM/HepSC axis in HIV/cART-induced liver diseases and suggest that inhibiting IFN-I signaling or M2LM may provide a novel therapeutic strategy for treating HIV/cART-associated liver diseases in PLWH treated with antiretroviral therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Type I interferons and TGF-β cooperate to induce liver fibrosis during HIV-1 infection under antiretroviral therapy

Ahodantin¹,

Nio²,

Funaki³

et al. 2022

JCI Insight

View full text Add to dashboard Cite

show abstract

“…Similarly, in chronic Staphylococcus aureus infection in mice, the survival rate was increased with SIRT2 deficiency ( 38 ), and in an SIRT2 −/− murine model, bacterial infections were reduced ( 37 ). More recently, in the context of HIV infection, the potential roles of SIRT2 in some HIV-associated comorbidities (insulin resistance and cardiovascular diseases), but also with neurocognitive disorders ( 39 ) and virus life cycle ( 40 ), have emerged. In particular, SIRT1, SIRT2, and SIRT3 can deacetylate and regulate Tat activity and, specifically for SIRT1, the interaction with Tat protein was shown to activate the HIV promoter ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction

Duran-Castells

Llano

Kawana-Tachikawa

et al. 2023

J Virol

View full text Add to dashboard Cite

Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control.

show abstract

“…SIRT1 downregulates DNL and gluconeogenesis improving the lipid and carbohydrate metabolism, and protecting the liver from steatosis ( 218 ). The inhibition of SIRT1 along with the decrease of adiponectin and leptin expression during HIV infection as well as during PIs treatment could represent one of the steps required for the development of HIV-associated NAFLD ( 219 ). On the other hand, experimental data suggest that HIV could promote the release of adiponectin ( 211 ).…”

Section: Hiv and Hbv Role In Nafld Pathogenesis And In The Breakdown ...mentioning

confidence: 99%

Non-Alcoholic Fatty Liver Disease in HIV/HBV Patients – a Metabolic Imbalance Aggravated by Antiretroviral Therapy and Perpetuated by the Hepatokine/Adipokine Axis Breakdown

Iacob

2022

Front. Endocrinol.

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with the metabolic syndrome and is one of the most prevalent comorbidities in HIV and HBV infected patients. HIV plays an early and direct role in the development of metabolic syndrome by disrupting the mechanism of adipogenesis and synthesis of adipokines. Adipokines, molecules that regulate the lipid metabolism, also contribute to the progression of NAFLD either directly or via hepatic organokines (hepatokines). Most hepatokines play a direct role in lipid homeostasis and liver inflammation but their role in the evolution of NAFLD is not well defined. The role of HBV in the pathogenesis of NAFLD is controversial. HBV has been previously associated with a decreased level of triglycerides and with a protective role against the development of steatosis and metabolic syndrome. At the same time HBV displays a high fibrogenetic and oncogenetic potential. In the HIV/HBV co-infection, the metabolic changes are initiated by mitochondrial dysfunction as well as by the fatty overload of the liver, two interconnected mechanisms. The evolution of NAFLD is further perpetuated by the inflammatory response to these viral agents and by the variable toxicity of the antiretroviral therapy. The current article discusses the pathogenic changes and the contribution of the hepatokine/adipokine axis in the development of NAFLD as well as the implications of HIV and HBV infection in the breakdown of the hepatokine/adipokine axis and NAFLD progression.

show abstract

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

Cited by 11 publications

References 173 publications

Type I interferons and TGF-β cooperate to induce liver fibrosis during HIV-1 infection under antiretroviral therapy

Type I interferons and TGF-β cooperate to induce liver fibrosis during HIV-1 infection under antiretroviral therapy

Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction

Non-Alcoholic Fatty Liver Disease in HIV/HBV Patients – a Metabolic Imbalance Aggravated by Antiretroviral Therapy and Perpetuated by the Hepatokine/Adipokine Axis Breakdown

Contact Info

Product

Resources

About