Gene Expression Signatures in AML-12 Hepatocyte Cells upon Dengue virus Infection and Acetaminophen Treatment.
Jorge G G FerreiraSandra Grossi GavaEneida S OliveiraIzabella C A BatistaGabriel da R FernandesMarina M MourãoCarlos Eduardo Calzavara-SilvaPublished in: Viruses (2020)
Dengue is an acute viral disease caused by Dengue virus (DENV) and is considered to be the most common arbovirus worldwide. The clinical characteristics of dengue may vary from asymptomatic to severe complications and severe organ impairment, particularly affecting the liver. Dengue treatment is palliative with acetaminophen (APAP), usually known as Paracetamol, being the most used drug aiming to relieve the mild symptoms of dengue. APAP is a safe and effective drug but, like dengue, can trigger the development of liver disorders. Given this scenario, it is necessary to investigate the effects of combining these two factors on hepatocyte homeostasis. Therefore, this study aimed to evaluate the molecular changes in hepatocytes resulting from the association between DENV infection and treatment with sub-toxic APAP concentrations. Using an in vitro experimental model of DENV-2 infected hepatocytes (AML-12 cells) treated with APAP, we evaluated the influence of the virus and drug association on the transcriptome of these hepatocytes by RNA sequencing (RNAseq). The virus-drug association was able to induce changes in the gene expression profile of AML-12 cells and here we highlight and explore these changes and its putative influence on biological processes for cellular homeostasis.
Keyphrases
- dengue virus
- zika virus
- aedes aegypti
- liver injury
- drug induced
- induced apoptosis
- gene expression
- acute myeloid leukemia
- cell cycle arrest
- genome wide
- single cell
- endoplasmic reticulum stress
- sars cov
- cell death
- emergency department
- cell proliferation
- intensive care unit
- risk factors
- combination therapy
- replacement therapy
- copy number
- palliative care
- acute respiratory distress syndrome
- respiratory failure
- extracorporeal membrane oxygenation
- hepatitis b virus