Search

Viral infections induce substantial metabolic changes in infected cells to optimize viral production while cells develop countermeasures to restrict that infection. Human respiratory syncytial virus (HRSV) is an infectious pathogen that causes severe lower respiratory tract infections (LRTI) in infants, the elderly, and immunocompromised adults for which no effective treatment or vaccine is currently available. In this study, variations in metabolite levels at different time points post-HRSV infection of epithelial cells were studied by untargeted metabolomics using liquid chromatography/mass spectrometry analysis of methanol cell extracts. Numerous metabolites were significantly upregulated after 18 hours post-infection, including nucleotides, amino acids, amino and nucleotide sugars, and metabolites of the central carbon pathway. In contrast, most lipid classes were downregulated. Additionally, increased levels of oxidized glutathione and polyamines were associated with oxidative stress in infected cells. These results show how HRSV infection influences cell metabolism to produce the energy and building blocks necessary for virus reproduction, suggesting potential therapeutic interventions against this virus. more...

The polymorphisms at the α-chain of the IL-7 receptor (IL7RA) have been related to T-cell homeostasis and development and may contribute to immune system deregulation. In the present study, we analyzed the association between IL7RA polymorphisms and the progression of liver fibrosis in patients infected with HCV. We carried out a retrospective study with a design consisting of repeated measurements in 187 HCV-infected patients, to study the risk prediction of liver fibrosis progression using genetic factors. We genotyped the rs6897932, rs987106 and rs3194051 IL7RA polymorphisms using the Agena Bioscience's MassARRAY. Transient elastography was used to measure liver stiffness. The used cut-offs were: 0.05). In univariate analysis, the rs6897932 T allele had a positive relationship with an increase in LSM (arithmetic mean ratio (AMR) = 1.21 (95%CI = 1.08; 1.36); p = 0.001), progression to advanced fibrosis (F≥3) (odds ratio (OR) = 2.51 (95%CI = 1.29; 4.88); p = 0.006) and progression to cirrhosis (F4) (OR = 2.71 (95%CI = 0.94; 5.03); p = 0.069). In multivariable analysis, the rs6897932 T allele was related to a higher increase of LSM values during follow-up (adjusted AMR = 1.27 (95%CI = 1.13; 1.42); p more...

The management of patients with chronic hepatitis C (CHC) depends on their clinical stage. Thus, noninvasive early recognition of patients with CHC at high risk for developing liver-related events (LREs) is important because it ensures optimal preventative management strategies may be employed that can affect the course of CHC disease. Our aim was to determine whether liver stiffness measurement (LSM) in hepatitis C virus (HCV)-infected patients is associated with a risk of LREs, particularly in cirrhotic patients. We carried out a retrospective study on 343 HCV-infected patients stratified according to cirrhosis (LSM more...

BACKGROUND:Resistance-associated variants have been related to treatment failure of hepatitis C virus (HCV) therapy with direct-acting antiviral drugs. The aim of our study was to analyze the prevalence of clinically relevant resistance-associated variants within NS3 in patients infected with HCV genotype 1a (GT1a) in Spain. METHODS:We performed a cross-sectional study on 2568 patients from 115 hospitals throughout Spain (2014-2015). The viral NS3 protease gene was amplified by nested polymerase chain reaction and sequenced by Sanger sequencing using an ABI PRISM 377 DNA sequencer. Additionally, clade information for genotype 1a was obtained by using the software geno2pheno (http://hcv.geno2pheno.org/). RESULTS:In total, 875 out of 2568 samples were from human immunodeficiency virus (HIV)/HCV-coinfected patients. Q80K was the main RAV found in our patients (11.1%) and the rest of the resistance-associated variants had a lower frequency, including S122G (6.23%), T54S (3.47%), V55A (2.61%), and V55I (2.15%), which were among the most frequent after Q80K. Overall, 286 samples had the Q80K polymorphism (11.1%) and 614 (23.9%) were GT1a clade I. HIV/HCV-coinfected patients had a higher frequency of Q80K and GT1a clade I than HCV-monoinfected patients (12.9% vs. 9.6% [p = 0.012] and 28.5% vs. 21.4% [p more...