Abstract
Micro RNAs (miRNAs) are essential players in HIV and HCV infections, as both viruses modulate cellular miRNAs and interact with the miRNA-mediated host response. We aim to analyze the miRNA profile of HIV patients with different exposure to HCV to explore specific signatures in the miRNA profile of PBMCs for each type of infection. We massively sequenced small RNAs of PBMCs from 117 HIV+ infected patients: 45 HIV+ patients chronically infected with HCV (HIV/HCV+), 36 HIV+ that spontaneously clarified HCV after acute infection (HIV/HCV-) and 36 HIV+ patients without previous HCV infection (HIV). Thirty-two healthy patients were used as healthy controls (HC). Differential expression analysis showed significantly differentially expressed (SDE) miRNAs in HIV/HCV+ (n = 153), HIV/HCV- (n = 169) and HIV (n = 153) patients. We found putative dysregulated pathways, such as infectious-related and PI3K signaling pathways, common in all contrasts. Specifically, putatively targeted genes involved in antifolate resistance (HIV/HV+), cancer-related pathways (HIV/HCV-) and HIF-signaling (HIV) were identified, among others. Our findings revealed that HCV strongly influences the expression profile of PBMCs from HIV patients through the disruption of its miRNome. Thus, different HCV exposure can be identified by specific miRNA signatures in PBMCs.
Highlights
2.75 million individuals worldwide are simultaneously coinfected with hepatitis C virus (HCV) and Human Immunodeficiency Virus (HIV), as both share common transmission routes (sexual and injection drug use (IDU) [1]
We explored the metabolic characteristics of the patients (Table 2), and we found differences regarding weight (p = 0.015) and body mass index (p = 0.026), where HIV/Hepatitis C Virus (HCV)+
Regarding the liver profile parameters, we found significant differences compared to healthy controls (HC) in: total cholesterol (TC), high-density lipoprotein (HDL) and atherogenic index of plasma (AIP) for patients in the HIV/HCV+
Summary
2.75 million individuals worldwide are simultaneously coinfected with hepatitis C virus (HCV) and HIV, as both share common transmission routes (sexual and injection drug use (IDU) [1]. HIV has a negative impact on the progression of HCV infection, and their natural history is altered in coinfection with HCV leading to a higher rate of cirrhosis, liver failure, and hepatocellular carcinoma, among others [2]. Acute infection is usually asymptomatic and 20–40% of infected persons spontaneously clear the virus within six months without treatment [3]. A clearance occurs more frequently in young people and women [4], besides a certain genetic predisposition, as people of African origin are less likely to clear HCV than those of Caucasian origin, the reasons for these differences are unclear. The rs12979860 CC genotype has been associated with a higher frequency of spontaneous HCV resolution
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