IFITM Proteins Restrict Antibody-Dependent Enhancement of Dengue Virus Infection

Interferon-inducible transmembrane (IFITM) proteins restrict the entry processes of several pathogenic viruses, including the flaviviruses West Nile virus and dengue virus (DENV). DENV infects cells directly or via antibody-dependent enhancement (ADE) in Fc-receptor-bearing cells, a process thought to contribute to severe disease in a secondary infection. Here we investigated whether ADE-mediated DENV infection bypasses IFITM-mediated restriction or whether IFITM proteins can be protective in a secondary infection. We observed that IFITM proteins restricted ADE-mediated and direct infection with comparable efficiencies in a myelogenous leukemia cell line. Our data suggest that IFITM proteins can contribute to control of secondary DENV infections

Event-by-event fluctuations of average transverse momentum in central Pb+Pb collisions at 158 GeV per nucleon

We present first data on event-by-event fluctuations in the average transverse momentum of charged particles produced in Pb+Pb collisions at the CERN SPS. This measurement provides previously unavailable information allowing sensitive tests of microscopic and thermodynamic collision models and to search for fluctuations expected to occur in the vicinity of the predicted QCD phase transition. We find that the observed variance of the event-by-event average transverse momentum is consistent with independent particle production modified by the known two-particle correlations due to quantum statistics and final state interactions and folded with the resolution of the NA49 apparatus. For two specific models of non-statistical fluctuations in transverse momentum limits are derived in terms of fluctuation amplitude. We show that a significant part of the parameter space for a model of isospin fluctuations predicted as a consequence of chiral symmetry restoration in a non-equilibrium scenario is excluded by our measurement.Comment: 6 pages, 2 figures, submitted to Phys. Lett.

Experimental Study of the Shortest Reset Word of Random Automata

In this paper we describe an approach to finding the shortest reset word of a finite synchronizing automaton by using a SAT solver. We use this approach to perform an experimental study of the length of the shortest reset word of a finite synchronizing automaton. The largest automata we considered had 100 states. The results of the experiments allow us to formulate a hypothesis that the length of the shortest reset word of a random finite automaton with $n$ states and 2 input letters with high probability is sublinear with respect to $n$ and can be estimated as $1.95 n^{0.55}.

Baryon Stopping and Charged Particle Distributions in Central Pb+Pb Collisions at 158 GeV per Nucleon

Net proton and negative hadron spectra for central \PbPb collisions at 158 GeV per nucleon at the CERN SPS were measured and compared to spectra from lighter systems. Net baryon distributions were derived from those of net protons, utilizing model calculations of isospin contributions as well as data and model calculations of strange baryon distributions. Stopping (rapidity shift with respect to the beam) and mean transverse momentum \meanpt of net baryons increase with system size. The rapidity density of negative hadrons scales with the number of participant nucleons for nuclear collisions, whereas their \meanpt is independent of system size. The \meanpt dependence upon particle mass and system size is consistent with larger transverse flow velocity at midrapidity for \PbPb compared to \SS central collisions.Comment: This version accepted for publication in PRL. 4 pages, 3 figures. Typos corrected, some paragraphs expanded in response to referee comments, to better explain details of analysi

Antibodies against Immature Virions Are Not a Discriminating Factor for Dengue Disease Severity

Humoral immunity plays an important role in controlling dengue virus (DENV) infection. Antibodies (Abs) developed during primary infection protect against subsequent infection with the same dengue serotype, but can enhance disease following secondary infection with a heterologous serotype. A DENV virion has two surface proteins, envelope protein E and (pre)-membrane protein (pr)M, and inefficient cleavage of the prM protein during maturation of progeny virions leads to the secretion of immature and partially immature particles. Interestingly, we and others found that historically regarded non-infectious prM-containing DENV particles can become highly infectious in the presence of E- and prM-Abs. Accordingly, we hypothesized that these virions contribute to the exacerbation of disease during secondary infection. Here, we tested this hypothesis and investigated the ability of acute sera of 30 DENV2-infected patients with different grades of disease severity, to bind, neutralize and/or enhance immature DENV2. We found that a significant fraction of serum Abs bind to the prM protein and to immature virions, but we observed no significant difference between the disease severity groups. Furthermore, functional analysis of the Abs did not underscore any specific correlation between the neutralizing/enhancing activity towards immature DENV2 and the development of more severe disease. Based on our analysis of acute sera, we conclude that Abs binding to immature virions are not a discriminating factor in dengue pathogenesis

Measurement of negative particle multiplicity in S - Pb collisions at 200 GeV/c per nucleon with the NA36 TPC

A high statistics study of the negative multiplicity distribution from S-Pb collisions at 200 GeV/c per nucleon is presented. The NA36 TPC was used to detect charged particles; corrections are based upon the maximum entropy method.A high statistics study of the negative multiplicity distribution from S-Pb collisions at 200 GeV/c per nucleon is presented. The NA36 TPC was used to detect charged particles; corrections are based upon the maximum entropy method.A high statistics study of the negative particle multiplicity distribution from S–Pb collisions at 200 GeV/ c per nucleon is presented. The NA36 TPC was used to detect charged particles; corrections are based upon the maximum entropy method

A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein

10.1371/journal.pone.0033451PLoS ONE74

In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection

Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization