Analysis of HIV-1 drug resistant mutations by line probe assay and direct sequencing in a cohort of therapy naive HIV-1 infected Italian patients

BACKGROUND: The routine determination of drug resistance in newly HIV-1 infected individuals documents a potential increase in the transmission of drug-resistant variants. Plasma samples from twenty seven therapy naive HIV-1 infected Italian patients were analyzed by the line probe assay (LIPA) and the TruGene HIV-1 assay for the detection of mutations conferring resistance to HIV-1. RESULTS: Both tests disclosed amino-acid substitutions associated with resistance in a variable number of patients. In particular, two mutations (K70R and V118I), detectable by LIPA and by sequencing analysis respectively, revealed resistance to NRTIs in two plasma samples. At least three mutations conferring resistance to NNRTIs, not detectable by commercial LIPA, able to reveal mutations associated only with nucleoside reverse transcriptase analogues, were disclosed by viral sequence analysis. Moreover, most samples showed mutations correlated with resistance to protease inhibitors. Remarkably, a key mutation, like V82A (found as a mixture), and some "indeterminate" results (9 samples), due the absence of signal on the lines corresponding to a specific probe, was revealed only by LIPA, while a variable number of secondary mutations was detectable only by TruGene HIV-1 assay. CONCLUSION: Even if further studies are necessary to establish the impact of different tests on the evaluation of drug-resistant strains transmission, LIPA might be useful in a wide population analysis, where bulk results are needed in a short time, while sequencing analysis, able to detect mutations conferring resistance to both NRTIs and NNRTIs, might be considered a more complete assay, albeit more expensive and more technically complex

Impact of the HIV-1 env Genetic Context outside HR1–HR2 on Resistance to the Fusion Inhibitor Enfuvirtide and Viral Infectivity in Clinical Isolates

Resistance mutations to the HIV-1 fusion inhibitor enfuvirtide emerge mainly within the drug's target region, HR1, and compensatory mutations have been described within HR2. The surrounding envelope (env) genetic context might also contribute to resistance, although to what extent and through which determinants remains elusive. To quantify the direct role of the env context in resistance to enfuvirtide and in viral infectivity, we compared enfuvirtide susceptibility and infectivity of recombinant viral pairs harboring the HR1–HR2 region or the full Env ectodomain of longitudinal env clones from 5 heavily treated patients failing enfuvirtide therapy. Prior to enfuvirtide treatment onset, no env carried known resistance mutations and full Env viruses were on average less susceptible than HR1–HR2 recombinants. All escape clones carried at least one of G36D, V38A, N42D and/or N43D/S in HR1, and accordingly, resistance increased 11- to 2800-fold relative to baseline. Resistance of full Env recombinant viruses was similar to resistance of their HR1–HR2 counterpart, indicating that HR1 and HR2 are the main contributors to resistance. Strictly X4 viruses were more resistant than strictly R5 viruses, while dual-tropic Envs featured similar resistance levels irrespective of the coreceptor expressed by the cell line used. Full Env recombinants from all patients gained infectivity under prolonged drug pressure; for HR1–HR2 viruses, infectivity remained steady for 3/5 patients, while for 2/5 patients, gains in infectivity paralleled those of the corresponding full Env recombinants, indicating that the env genetic context accounts mainly for infectivity adjustments. Phylogenetic analyses revealed that quasispecies selection is a step-wise process where selection of enfuvirtide resistance is a dominant factor early during therapy, while increased infectivity is the prominent driver under prolonged therapy

Design status of ASPIICS, an externally occulted coronagraph for PROBA-3

The "sonic region" of the Sun corona remains extremely difficult to observe with spatial resolution and sensitivity sufficient to understand the fine scale phenomena that govern the quiescent solar corona, as well as phenomena that lead to coronal mass ejections (CMEs), which influence space weather. Improvement on this front requires eclipse-like conditions over long observation times. The space-borne coronagraphs flown so far provided a continuous coverage of the external parts of the corona but their over-occulting system did not permit to analyse the part of the white-light corona where the main coronal mass is concentrated. The proposed PROBA-3 Coronagraph System, also known as ASPIICS (Association of Spacecraft for Polarimetric and Imaging Investigation of the Corona of the Sun), with its novel design, will be the first space coronagraph to cover the range of radial distances between ~1.08 and 3 solar radii where the magnetic field plays a crucial role in the coronal dynamics, thus providing continuous observational conditions very close to those during a total solar eclipse. PROBA-3 is first a mission devoted to the in-orbit demonstration of precise formation flying techniques and technologies for future European missions, which will fly ASPIICS as primary payload. The instrument is distributed over two satellites flying in formation (approx. 150m apart) to form a giant coronagraph capable of producing a nearly perfect eclipse allowing observing the sun corona closer to the rim than ever before. The coronagraph instrument is developed by a large European consortium including about 20 partners from 7 countries under the auspices of the European Space Agency. This paper is reviewing the recent improvements and design updates of the ASPIICS instrument as it is stepping into the detailed design phase

Straylight analysis of the external baffle of COROT

The COROT mission is part of the program "mini-satellite" of CNES (French space agency). It implies international cooperation between European institutes and research centres. COROT aims to perform astroseismology observations and to detect exoplanets. Long duration observations of stars will be used to detect periodic variations with an afocal telescope followed by a dioptric objective and 4 CCDs. These very small variations can be caused by star seismic activities (about 10-6 variation of signal) or transits of planets (few 10-4 variation of signal). Due to the orbit of the spacecraft (low altitude polar orbit) and even if the observations are performed in a direction perpendicular to orbit plane, the measurements can be disturbed by the straylight reflected by the earth (albedo) that can generate a periodic perturbation. The paper details the overall optical design of the baffle. The baffle modelling and straylight computation methods are described and the expected performances are discussed. © 2017 SPIE

Optical modeling for the LiteBIRD Medium and High Frequency Telescope

International audienceLiteBIRD is the next-generation space mission for polarization-sensitive mapping of the Cosmic Microwave Background anisotropies, with observations covering the full sky in a wide frequency range (34-448 GHz) to ensure high-precision removal of polarized foregrounds. Its main goal is to constrain the contribution of primordial gravitational waves to the curly component of the CMB polarization pattern. The LiteBIRD Medium and High Frequency Telescope (MHFT) will observe the sky in the 89-448 GHz band. Its optical configuration features two separate dual-lens assemblies with 300mm and 200mm apertures, 28° fields of view and diffraction-limited imaging over the whole spectral range. Polarization modulation is achieved through the continuous spinning of a half-wave plate at the optical entrance of each system. The optical studies for MHFT focus on a refined modeling of the telescope elements (lenses, anti-reflection coatings, absorbers, interfaces) to assess their individual effects on the predicted optical behavior of the telescopes. Such studies will provide key inputs for end-to-end simulations and will inform the subsystem and system-level characterization to meet the stringent requirements set for the LiteBIRD success. We describe the progress in MHFT optical modeling and the ongoing efforts to reproduce full Medium Frequency Telescope (MFT) and High Frequency Telescope (HFT) beams for representative focal plane pixels down to the far-sidelobe angular region. Here, systematic effects due to challenging beam measurements and higher order optical coupling between the telescope and the surrounding structures are likely to affect the final level and shape of the beams and thus set compelling requirements for in-flight calibration and beam reconstruction

The CoRoT satellite in flight: description and performance

International audienceContext. CoRoT is a space telescope dedicated to stellar seismology and the search for extrasolar planets. The mission is led by the CNES in association with French laboratories and has a large international participation. The European Space Agency (ESA), Austria, Belgium, and Germany contribute to the payload, and Spain and Brazil contribute to the ground segment. Development of the spacecraft, which is based on a PROTEUS low earth orbit (LEO) recurrent platform, commenced in October 2000, and the satellite was launched on December 27, 2006. Aims. The instrument and platform characteristics prior to launch have been described in ESA publication (SP-1306). In the present paper we explain the behaviour in flight, based on raw and corrected data. Methods. Five runs have been completed since January 2007. The data used here are essentially those acquired during the commissioning phase and from a long run that lasted 146 days. These enable us to give a complete overview of the instrument and platform behaviour for all environmental conditions. The ground based data processing is not described in detail because the most important method has been published elsewhere. Results. We show that the performance specifications are easily satisfied when the environmental conditions are favourable. Most of the perturbations, hence data corrections, are related to LEO perturbations: high energy particles inside the South Atlantic Anomaly (SAA), eclipses and temperature variations, and line of sight fluctuations due to the attitude control system. Straylight due to the reflected light from the earth, which is controlled by the telescope and baffle design, appears to be negligible

The Solar Orbiter EUI instrument: The Extreme Ultraviolet Imager

Context. The Extreme Ultraviolet Imager (EUI) is part of the remote sensing instrument package of the ESA/NASA Solar Orbiter mission that will explore the inner heliosphere and observe the Sun from vantage points close to the Sun and out of the ecliptic. Solar Orbiter will advance the "connection science" between solar activity and the heliosphere. Aims: With EUI we aim to improve our understanding of the structure and dynamics of the solar atmosphere, globally as well as at high resolution, and from high solar latitude perspectives. Methods: The EUI consists of three telescopes, the Full Sun Imager and two High Resolution Imagers, which are optimised to image in Lyman-α and EUV (17.4 nm, 30.4 nm) to provide a coverage from chromosphere up to corona. The EUI is designed to cope with the strong constraints imposed by the Solar Orbiter mission characteristics. Limited telemetry availability is compensated by state-of-the-art image compression, onboard image processing, and event selection. The imposed power limitations and potentially harsh radiation environment necessitate the use of novel CMOS sensors. As the unobstructed field of view of the telescopes needs to protrude through the spacecraft's heat shield, the apertures have been kept as small as possible, without compromising optical performance. This led to a systematic effort to optimise the throughput of every optical element and the reduction of noise levels in the sensor. Results: In this paper we review the design of the two elements of the EUI instrument: the Optical Bench System and the Common Electronic Box. Particular attention is also given to the onboard software, the intended operations, the ground software, and the foreseen data products. Conclusions: The EUI will bring unique science opportunities thanks to its specific design, its viewpoint, and to the planned synergies with the other Solar Orbiter instruments. In particular, we highlight science opportunities brought by the out-of-ecliptic vantage point of the solar poles, the high-resolution imaging of the high chromosphere and corona, and the connection to the outer corona as observed by coronagraphs