HIV Evolution in Early Infection: Selection Pressures, Patterns of Insertion and Deletion, and the Impact of APOBEC

The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not of mutational hotspots. Our results provide a detailed view of the process of diversification of HIV-1 following transmission, highlighting the role of CTL escape and hypermutation in shaping viral evolution during the establishment of new infections

Provenance evolution of the northern Weihe Basin as an indicator of environmental changes during the Quaternary

© Cambridge University Press 2019. The Weihe Basin is an intracontinental rift basin in central China that provides an ideal location for studying the interactions between regional tectonics and monsoonal climate change. In this paper, we present detrital zircon U-Pb ages from sediments from Core LYH drilled in the northern margin of the basin. We use these to illuminate changing sediment transport processes, provenance and palaeo-environments during the Quaternary. The sediments are dominated by zircon age groups of 100-400 Ma and 400-550 Ma, and three secondary age peaks at 700-1100 Ma, 1700-2100 Ma and 2400-2600 Ma. Multidimensional scaling plots support the conclusion that the Central Loess Plateau and the Luo River are the dominant sources of sediments to the core site. Before c. 1.06 Ma, the Qinling Mountains and the Wei River, as well as the Yellow River, had minor influence on the sedimentation at the core site. These results are consistent with the existence of a palaeolake prior to 1.06 Ma, which allowed sediments supplied to the south and east edge of the basin to be reworked to the northern side of the Weihe Basin. Subsequently, the Luo River has provided a steady source of sediments to the northern Weihe Basin

Chemotactic properties of rat immunoglobulins and immune complexes.

The effect of rat immunoglobulins and immune complexes on the locomotor function of rat polymorphonuclear leukocytes (PMN) was investigated in vitro. Rat immunoglobulin G1 (IgG1), IgG2a, IgG2b, and IgA monoclonal antibodies specific for the dinitrophenyl hapten were used. Both monomeric and polymeric IgA showed chemotactic activity in a dose-dependent manner. IgG1 and IgG2b also induced a dose-dependent locomotor response of PMN, but the nature of the induced migration was chemokinetic (enhancing random migration). IgG2a was chemotactic and induced maximal migration at a relatively low concentration. IgG1- and IgG2b-immune complexes induced stronger migration than antibody alone; however, IgA- and IgG2a-immune complexes did not. IgA was shown to modify the chemotactic movement of PMN induced by N-formylmethionyl-leucyl-phenylalanine (FMLP). In the presence of both IgA and FMLP in the lower chamber, the migration towards suboptimal concentrations of FMLP was enhanced. By contrast, IgA in the upper chamber decreased migration towards the optimal or higher concentrations of FMLP. These findings suggest that IgA may work synergistically with luminal chemoattractants to mobilize PMN to the locus of infection on the mucosal surface. In addition, the intense activity of IgG2a alone and IgG1- or IgG2b-immune complexes in inducing PMN migration may play an important role in inflammatory processes. The data indicate that immunoglobulins have a direct effect on PMN mobility

Star in the sky. The SMOS payload: MIRAS

7 pages, 5 figures, 2 boxes.-- Reprinted from ESA BulletinMIRAS is more than just the payload of SMOS. It is a radio telescope pointed towards Earth, an instrument that has challenged the fundamental theories of radio astronomy, and made a major contribution to science even before being launched.Built by a consortium of over 20 European companies led by EADS-CASA Espacio (E), MIRAS is the single instrument carried on board ESA’s Soil Moisture and Ocean Salinity (SMOS) mission. MIRAS stands for the Microwave Imaging Radiometer with Aperture Synthesis.The theory behind microwave remote sensing of soil moisture and ocean salinity is based on the significant contrast between the electromagnetic properties of pure liquid water and dry soil, and pure water and saline water respectively. As the proportion of water in the soilwater mixture (or proportion of salt in the saline mixture) increases, this change is detectable by microwave sensors in terms of the emission of microwave energy, called the ‘microwave brightness temperature’ of the surfacePeer reviewe

Verifying Cryptographic Protocols with Subterms Constraints

The original publication is available at www.springerlink.comInternational audienceKnown protocol analysis techniques consider protocols where some piece of information expected in a protocol message is located at a fixed position. However this is too restrictive to model web-services where messages are XML semi-structured documents and where significant information (such as name, signature, ...) has to be extracted from nodes occurring at flexible positions. Therefore we have extended the Dolev Yao model by a subterm predicate that allows one to express data extraction by subterm matching. This also allows one to detect so-called rewriting attacks that are specific to web-services.Nous étudions les protocoles utilisant une opération d'extraction de sous-message par filtrage, utilisée par exemple dans les web-services et proposons une procédure de détection des attaques par réécriture pour ces protocoles