Affiliation:
1. Viral Hepatitis Reference and Research Laboratory, National Center of Microbiology Institute of Health Carlos III Madrid Majadahonda Spain
2. Internal Medicine Service La Paz University Hospital (IdiPAZ) Madrid Spain
3. VIH Unit, Internal Medicine Service Doce de Octubre Hospital Biomedical Research Institute (imas12) Madrid Spain
4. King's College London University London UK
5. Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC) Institute of Health Carlos III Madrid Spain
6. Department of Infectious Diseases, HIV/Hepatitis Internal Medicine Service Infanta Leonor University Hospital Madrid España
7. Internal Medicine—Infectious Diseases Service La Princesa University Hospital Madrid España
Abstract
AbstractCoinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls. Oxidative stress biomarkers were analyzed at lipid, DNA, protein, and nitrates levels, as well as antioxidant capacity and glutathione reductase enzyme. Replicative senescence was evaluated by relative telomere length (RTL) measurement. Additionally, 26 markers of Senescence‐Associated Secretory Phenotype (SASP) were analyzed by multiplex immunoassays (Luminex xMAP technology). Differences were evaluated by generalized linear model (GLMs) adjusted by most significant covariates. The SC group had a senescence signature similar to the HIV control group and slightly lower SASP levels. However, significant differences were observed with respect to the CHC group, where an increase in the nitrate concentration [adjusted arithmetic mean ratio, aAMR = 1.73 (1.27–2.35), p < 0.001, q = 0.009] and the secretion of 13 SASP‐associated factors [granulocyte macrophage colony‐stimulating factor (GM‐CSF), interferon‐β, interleukin (IL)‐1β, IL‐2, IL‐8, IL‐13, tumor necrosis factor (TNF)‐α, IL‐1α, IL‐1RA, IL‐7, IL‐15, C‐X‐C motif chemokine ligand 10 (IP‐10), stem cell factor (SCF); q < 0.1)] was detected. The CHC group also showed higher values of IL‐1α, IP‐10, and placental growth factor 1 (PIGF‐1) than HIV controls. The SC group showed a slightly lower senescence profile than the HIV group, which could indicate a more efficient control of viral‐induced senescence due to their immune strengths. Chronic HCV infection in PLWHIV led to an increase in nitrate and elevated SASP biomarkers favoring the establishment of viral persistence.
Subject
Infectious Diseases,Virology
Cited by
1 articles.
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