Mécanismes immunologiques impliqués dans la persistance des réservoirs du VIH.

Résumé Les thérapies antirétrovirales (TAR) permettent de contrôler la réplication virale et ont considérablement amélioré la qualité et l'espérance de vie des personnes vivant avec le VIH (PVVIH). Toutefois, près de 40 ans après la découverte du virus, il n'existe toujours pas de traitement curatif permettant d'éliminer le VIH de l'organisme : Même après des années de TAR efficace, le virus persiste dans des cellules, principalement des lymphocytes T CD4 mémoires, qui constituent une source pérenne de virus infectieux et qui nécessitent de poursuivre les traitements à vie. Les recherches sur les réservoirs du VIH menées au cours des 25 dernières années ont permis de mieux comprendre comment certaines cellules infectées persistent pendant des décennies sans être éliminées, ni par les TAR, ni par les réponses immunitaires. Le VIH « se cache ¼ dans des cellules à durée de vie très longue, qui ont la capacité de proliférer par différents mécanismes et qui expriment préférentiellement certains récepteurs leur permettant de demeurer invisibles au système immunitaire. Une meilleure compréhension de ces mécanismes de persistance est un prérequis nécessaire à la mise au point de stratégies thérapeutiques visant à éradiquer le VIH.

Immunological mechanisms involved in the persistence of HIV reservoirs.

Antiretroviral therapy (ART) controls viral replication and has dramatically improved the quality and life expectancy of people living with HIV (PLHIV). However, almost 40 years after the discovery of HIV, there is still no cure; even after years of effective ART, the virus persists in cells, primarily memory CD4 T cells. These cells are a perennial source of infectious viruses, which necessitate that people living with HIV continue ART for life. Research on HIV reservoirs over the past 25 years has provided insight into how some infected cells persist for decades without being cleared by ART nor by immune responses. HIV "hides" in cells with extended lifespans, which have the capacity to proliferate through diverse mechanisms and which preferentially express several receptors that allow them to remain invisible to the immune system. A better understanding of these mechanisms of persistence is a necessary prerequisite for the development of therapeutic strategies aimed at eradicating HIV.

Monocyte Gene and Molecular Expression Profiles Suggest Distinct Effector and Regulatory Functions in Beninese HIV Highly Exposed Seronegative Female Commercial Sex Workers.

We have previously reported that the female genital tract (FGT) of Beninese HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs), presented elevated frequencies of a myeloid HLA-DR+CD14+CD11c+ population presenting "tolerogenic" monocyte derived dendritic cells (MoDC) features. In order to assess whether a differential profile of monocytes may be involved in the generation of these genital MoDCs, we have herein characterized the blood monocyte compartment of Beninese HESNs (HIV-uninfected ≥ 10 years CSWs) and relevant controls (HIV-uninfected 2.5-5 years CSWs herein termed "early HESNs"), HIV-infected CSWs, and low-risk HIV-uninfected women from the general population. Transcriptomic analyses by RNA-Seq of total sorted blood monocytes demonstrate that in comparison to the control groups, HESNs present increased expression levels of FCGR2C, FCAR, ITGAX, ITGAM, CR2, CD68, and CD163 genes, associated with effector functions. Moreover, we found increased expression levels of genes associated with protection/control against SHIV/HIV such as CCL3, CCL4, CCL5, BHLHE40, and TNFSF13, as well as with immune regulation such as IL-10, Ahr, CD83, and the orphan nuclear receptor (NR)4A1, NR4A2, and NR4A3. Through multicolor flow cytometry analyses, we noticed that the frequencies of intermediate and non-classical monocyte populations tended to be elevated in the blood of HESNs, and exhibited increased expression levels of effector CD16, CD11c, CD11b, as well as regulatory HLA-G, IL-10, and IFN-α markers when compared to HIV-uninfected women and/or HIV-infected CSWs. This profile is compatible with that previously reported in the FGT of HESNs, and likely confers an enormous advantage in their resistance to HIV infection.

Proximal and distal radial artery approaches for endovascular percutaneous procedures: anatomical suitability by ultrasound evaluation.

PURPOSE: To describe the variability of the radial artery (RA) diameters at 2 levels, proximal (pRA), within 2 cm to the styloid process, and distal (dRA) at the snuff box, both eligible accesses for percutaneous approach, and to correlate these diameters with population features. METHODS: A total of 700 patients (377 females, 323 males) have been enrolled from July 2018 to March 2019. The diameters of left and right RA were measured using ultrasound (US) examination. Diameters of pRA and dRA were compared between different sex and CRF (tabagism, hypertension, hyperlipidemia, BMI > 30, diabetes) using multivariate analysis and unpaired t test; the feasibility of radial access was evaluated considering a diameter ≥ of 2 mm as a cut-off or a vessel/sheath ratio >1. The time needed to perform each assessment of the four vessels was recorded. RESULTS: The average proximal diameter of pRA was 2.58 mm (sd = 0.58 mm). The caliber of the dRA resulted 19.5% lower than the proximal one, with an average diameter of 1.99 mm (sd = 0.47 mm). On unpaired t test, a significant difference was reported for two of the parameters taken into account: sex and a BMI > 30. CONCLUSION: Our results show that 88% of patients have an estimated radial artery caliber suitable for pTRA at US examination. Males and patients with BMI > 30 show a higher mean pRA and dRA; thus, they could be the ideal candidates for radial access.

Sequential, co-registered fluorine and proton field-cycled Overhauser imaging at a detection field of 59 mT.

In this work we show the feasibility of sequential, co-registered fluorine and proton field-cycled Overhauser imaging at a detection field of 59 mT. To this purpose we have built an RF coil assembly comprising an Alderman-Grant resonator for EPR irradiation at 127.7 MHz (evolution field of 4.5 mT) and a solenoidal coil for (19)F or (1)H MRI acquisition at the detection field of 59 mT. A removable tuning/matching circuit that allows the solenoid to be tuned to the (19)F frequency (2.346 MHz, FEDRI) or the (1)H frequency (2.494 MHz, PEDRI) without removing the sample was built and tested. Switching of the solenoid between the (19)F and (1)H frequency is thus achieved in less than 1 min. The co-registered FC-FEDRI and FC-PEDRI images show higher enhancement in the sample regions with higher free radical concentration. This work is the first methodological step towards the development of an MRI scanner capable of acquiring morphological ((1)H) and physiological ((19)F) images in animal models at very low fields.