Circulating microRNAs as non-invasive biomarkers for hepatitis B virus liver fibrosis.

Viruses can alter the expression of host microRNAs (MiRNA s) and modulate the immune response during a persistent infection. The dysregulation of host MiRNA s by hepatitis B virus (HBV) contributes to the proinflammatory and profibrotic changes within the liver. Multiple studies have documented the differential regulation of intracellular and circulating MiRNA s during different stages of HBV infection. Circulating MiRNA s found in plasma and/or extracellular vesicles can integrate data on viral-host interactions and on the associated liver injury. Hence, the detection of circulating MiRNA s in chronic HBV hepatitis could offer a promising alternative to liver biopsy, as their expression is associated with HBV replication, the progression of liver fibrosis, and the outcome of antiviral treatment. The current review explores the available data on miRNA involvement in HBV pathogenesis with an emphasis on their potential use as biomarkers for liver fibrosis.

Neurocognitive Impairment in the Combined Antiretroviral Therapy Era in a Romanian Cohort of Young Adults with Chronic HIV Infection.

HIV-associated neurocognitive disorders (HAND) continue to be reported even in patients with successful antiretroviral treatment. We investigated the prevalence of neurocognitive impairment and possible HIV-associated determinants of cognition in a Romanian cohort of young adults, parenterally infected with HIV during their first years of life. Two hundred fourteen treatment-experienced HIV-positive individuals [median age: 24 years, males: 48%, median duration on combined antiretroviral therapy (cART): 12 years] underwent standard immunologic and virological monitoring and antiretroviral resistance testing using pol gene sequencing in both plasma and, when available, cerebrospinal fluid (CSF) paired samples. Neurocognitive impairment was assessed using a comprehensive neuropsychological test battery, and a global deficit score (GDS) was calculated (cutoff ≥0.5). Cognitive impairment was detected in 35% of the study participants, without any association with sex, median age, CD4 cell count (actual or nadir), CSF and plasma viral load (actual or zenith), AIDS diagnosis, duration of HIV infection, and cART characteristics. Participants carrying resistant viruses tended to be more frequently cognitively impaired (p = 0.36), with a higher median GDS value (p = 0.06) compared with participants harboring wild-type HIV, although the figures did not reach statistical significance. No signs of virological compartmentalization were observed based on CSF versus plasma viral load and on the profile of pol sequences. A moderate rate of mild neurocognitive impairment is still present in young adults with chronic HIV infection acquired in early childhood despite successful cART, without any association with classic markers of HIV infection. New biomarkers reflecting persistent central nervous system inflammation and neuronal injury may be more relevant for the development of HAND.

Extracellular RNA in viral-host interactions: Thinking outside the cell.

Small RNAs and their associated RNA interference (RNAi) pathways underpin diverse mechanisms of gene regulation and genome defense across all three kingdoms of life and are integral to virus-host interactions. In plants, fungi and many animals, an ancestral RNAi pathway exists as a host defense mechanism whereby viral double-stranded RNA is processed to small RNAs that enable recognition and degradation of the virus. While this antiviral RNAi pathway is not generally thought to be present in mammals, other RNAi mechanisms can influence infection through both viral- and host-derived small RNAs. Furthermore, a burgeoning body of data suggests that small RNAs in mammals can function in a non-cell autonomous manner to play various roles in cell-to-cell communication and disease through their transport in extracellular vesicles. While vesicular small RNAs have not been proposed as an antiviral defense pathway per se, there is increasing evidence that the export of host- or viral-derived RNAs from infected cells can influence various aspects of the infection process. This review discusses the current knowledge of extracellular RNA functions in viral infection and the technical challenges surrounding this field of research. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action.

Immunoassay and molecular methods to investigate DNA methylation changes in peripheral blood mononuclear cells in HIV infected patients on cART.

This study aimed to investigate the influence of antiretroviral therapy on methylation markers, in a group of HIV infected, heavily treated patients. Immune and molecular methods were used to investigate potential changes in methylation profile in DNA isolated from peripheral blood mononuclear cells collected from antiretroviral-experienced HIV infected patients and healthy controls. The percentage of 5-methylcytosine was inversely correlated with proviral DNA and active replication while DNMT1 (p = 0.01) and DNMT3A (p = 0.004) independently correlated with active viral replication. DNMT3A expression increased with total treatment duration (p = 0.03), number of antiretroviral drugs ever used (p = 0.003), and cumulative exposure to protease inhibitors (p = 0.02) even in currently HIV undetectable patients.

miR-29a associates with viro-immunological markers of HIV infection in treatment experienced patients.

MicroRNAs (miRNAs) are small, non-coding RNA species essential for the post-translational regulation of gene expression. Several miRNA have been proposed to contribute to Human immunodeficiency virus-1 (HIV-1) infection establishment, progression and latency. Among them, miR-29a seems to be of particular interest. The aim of this study was to investigate the association between miR-29a expression and immunologic and virologic markers of HIV infection progression in long-term antiretroviral-treated individuals. In a homogenous group of 165 young adults, with chronic HIV infection, parenterally acquired during childhood, the expression level of miR-29a was found to be inversely correlated with HIV viral load and the degree of immunosuppression, expressed by both CD4 cell count and the CD4/CD8 ratio. There was a significant difference in miR-29a expression according to the patient's response to treatment, with the lowest levels expressed by patients with treatment failure, defined as detectable viremia and CD4 < 350 cells/mm3 . No significant correlation was found between miRNA level and the nadir CD4 count or zenith HIV viral load. This study establishes the association between miR-29a expression and markers of HIV infection in long-term survivors, treatment-experienced patients, suggesting its potential use as an indicator for the on-treatment disease evolution. J. Med. Virol. 88:2132-2137, 2016. © 2016 Wiley Periodicals, Inc.

MICRORNA BIOGENESIS AND ITS ROLE IN HIV-1 INFECTION.

MicroRNA (miRNA) are small- 19-24 nucleotides, non-coding RNA molecules that regulate translational and post-translational processes through mRNA degradation and protein translation repression, or sometimes through heterochromatin formation or activation of protein translation. Lately, miRNA are investigated as predictive biomarkers for the evolution and prognosis of viral diseases, as well as therapeutic targets. Although the role of non-coding RNA molecules during HIV infection is not yet fully elucidated, several studies have reported strong correlations between cellular and viral miRNA expression and the immunologic and virological status of infected patients. Some studies have proven the existence of host cellular miRNA able to influence all important steps in HIV replicative cycle and to interfere with the establishment of latent infection in CD4+ cells. Although the function and existence of viral encoded miRNA remains controversial, new studies have shown their potential in modulating the host cell response or the efficiency of viral replication. This review aims to summarize the current level of knowledge in the interaction between miRNA and HIV-1 and to describe new therapeutic strategies entailing miRNAs as new and potent players in controlling viral infectivity, replication and latency.