MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection

Factors involved in the spontaneous cleareance of a hepatitis C (HCV) infection are related to both HCV and the interaction with the host immune system, but little is known about the consequences after a spontaneous resolution. The main HCV extrahepatic reservoir is the peripheral blood mononuclear cells (PBMCs), and their transcriptional profile provides us information of innate and adaptive immune responses against an HCV infection. MicroRNAs regulate the innate and adaptive immune responses, and they are actively involved in the HCV cycle. High Throughput sequencing was used to analyze the miRNA profiles from PBMCs of HCV chronic naïve patients (CHC), individuals that spontaneously clarified HCV (SC), and healthy controls (HC). We did not find any differentially expressed miRNAs between SC and CHC. However, both groups showed similar expression differences (21 miRNAs) with respect to HC. This miRNA signature correctly classifies HCV-exposed (CHC and SC) vs. HC, with the has-miR-21-3p showing the best performance. The potentially targeted molecular pathways by these 21 miRNAs mainly belong to fatty acids pathways, although hippo signaling, extracellular matrix (ECM) interaction, proteoglycans-related, and steroid biosynthesis pathways were also altered. These miRNAs target host genes involved in an HCV infection. Thus, an HCV infection promotes molecular alterations in PBMCs that can be detected after an HCV spontaneous resolution, and the 21-miRNA signature is able to identify HCV-exposed patients (either CHC or SC).Funding: This work has been funded by the Instituto de Salud Carlos III (Subdirección General de Evaluación) (grant number CP14/0010) Fondo de Investigación Sanitaria (FIS) (grant numbers MPY 1404/15, MPY 1144/16, and MPY 382/18), and Integrated Projects of Excellence (grant number PIE15/00079).S

HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study

In HIV-1/HCV-coinfected patients, chronic HCV infection leads to an increased T-lymphocyte immune activation compared to HIV-monoinfected patients, thereby likely contributing to increase HIV-1 reservoir that is the major barrier for its eradication. Our objective was to evaluate the influence of HCV coinfection in HIV-1 viral reservoir size in resting (r) CD4+ T-cells (CD25-CD69-HLADR-). Multicenter cross-sectional study of 97 cART-treated HIV-1 patients, including 36 patients with HIV and HCV-chronic co-infection without anti-HCV treatment, 32 HIV patients with HCV spontaneous clearance and 29 HIV-monoinfected patients. rCD4+ T-cells were isolated and total DNA was extracted. HIV viral reservoir was measured by Alu-LTR qPCR. Differences between groups were calculated with a generalized linear model. Overall, 63.9% were men, median age of 41 years and Caucasian. Median CD4+ and CD8+ T-lymphocytes were 725 and 858 cells/mm 3 , respectively. CD4+ T nadir cells was 305 cells/mm 3 . Proviral HIV-1 DNA size was significantly increased in chronic HIV/HCV-coinfected compared to HIV-monoinfected patients (206.21 ± 47.38 vs. 87.34 ± 22.46, respectively; P = 0.009), as well as in spontaneously clarified HCV co-infected patients when compared to HIV-monoinfected individuals (136.20 ± 33.20; P = 0.009). HIV-1/HCV co-infected patients showed a larger HIV-1 reservoir size in comparison to HIV-monoinfected individuals. This increase could lead to a greater complexity in the elimination of HIV-1 reservoir in HIV-1/HCV-coinfected individuals, which should be considered in the current strategies for the elimination of HIV-1 reservoir.Financial support was provided by the Instituto de Salud Carlos III to VB (PI15CIII/00031), by the Spanish Ministry of Economy and Competitiveness to MC (SAF2016–78480-R) and The SPANISH AIDS Research Network RD16CIII/0002/0001, RD16CIII/0002/0002 and RD16/0025/0013 - ISCIII – FEDER. MRLP is supported by ISCIII - Subdirección General de Evaluacion and European Funding for Regional Development (FEDER) (PIE 13/00040 and RD12/0017/0017 RETIC de SIDA). C.P. is supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT) (grant number SFRH/ BPD/77448/2011 is part of the EDCTP2 programme supported by the European Union). V.B., A.F.R. and N.R. are supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII) (grant number CP13/00098, CP14/CIII/00010 and CP14/00198, respectively)

Different HCV Exposure Drives Specific miRNA Profile in PBMCs of HIV Patients

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.This work has been supported by grants from Institute of Health Carlos III, [PI15CIII/00031 and PI18CIII/00020/ to AFR and VB] and the Foundation Universidad Alfonso X el Sabio-Santander [grant number 1.010.932 to AFR] and the Spanish AIDS Research Network (RD16CIII/0002/0002), and Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas (CB21/13/00044). AFR is supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII) [CP14/CIII/00010 and CPII20CIII/0001].info:eu-repo/semantics/publishedVersio

MSGLib: A Modelica library for message passing communication

MSGLib is a Modelica library designed and developed to support message passing communication and the management of data structures stored in dynamic memory. The functionality of the library facilitates the description of discrete-event models and their combination with other Modelica functionality. MSGLib has been used as a base to develop other Modelica libraries such as DEVSLib, ARENALib and ABMLib. A new version of MSGLib is presented in this manuscript, that includes user documentation, performance optimization and illustrative examples. The library has been developed and tested under Dymola and OpenModelica, and is freely distributed under the LGPL-3.0 license

An approach to agent-based modeling with Modelica

Modelica is a free, general-purpose object-oriented equation-based modeling language. It is mainly designed to describe systems using the physical modeling approach. Our proposal to describe Agent-Based Models (ABMs) in Modelica is discussed in this manuscript. The contribution of the presented work is twofold: firstly, to analyze the conceptual requirements to describe ABMs in Modelica; and secondly, to develop a prototype implementation following the previous analysis. Agents are described using a message passing communication mechanism previously proposed by the authors. Additional extensions to this mechanism are proposed in order to describe agent interactions. The environment, where the agents live, is described as a two-dimensional cellular automaton. A new Modelica library, named ABMLib, developed to support this functionality, is presented. A prototype implementation of the message passing mechanism and ABMLib models has been performed to demonstrate the functionality of the library as a proof-of-concept for this proposal.Fil: Sanz, Victorino. Universidad Nacional de Educación a Distancia; EspañaFil: Bergero, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; ArgentinaFil: Urquia, Alfonso. Universidad Nacional de Educación a Distancia; Españ

CellularAutomataLib2: improving the support for cellular automata modelling in Modelica

CellularAutomataLib is a library developed by the authors to facilitate the description of Cellular Automata (CA) models in Modelica. It supports the description of 1D and 2D CA and their combination with other Modelica models. Modelling versatility and scalability are the main focus in the design. The internal behaviour of CA models is programmed in C, that is consequently hidden to the modelling tool and not considered in the causalization and manipulation of the model. A new version, named CellularAutomataLib2, is presented in this manuscript. The library has been extended to improve the simulation performance, by only evaluating active cells, and to support Lattice Gas Cellular Automata (LGCA) models. The library design and use are discussed. Two models, forest fire spread and the ARGESIM C17 ‘SIR-type Epidemic Spread’, are used to illustrate the functionality of the library. CellularAutomataLib2 is freely available at http://www.euclides.dia.uned.es (under the Modelica License 2)