Human immunodeficiency virus type-1 (HIV-1) continues to evolve in presence of broadly neutralizing antibodies more than ten years after infection.

BACKGROUND: The evolution of HIV-1 and its immune escape to autologous neutralizing antibodies (Nabs) during the acute/early phases of infection have been analyzed in depth in many studies. In contrast, little is known about neither the long-term evolution of the virus in patients who developed broadly Nabs (bNabs) or the mechanism of escape in presence of these bNabs. RESULTS: We have studied the viral population infecting a long term non progressor HIV-1 infected patient who had developed broadly neutralizing antibodies toward all tier 2/3 viruses (6 clades) tested, 9 years after infection, and was then followed up over 7 years. The autologous neutralization titers of the sequential sera toward env variants representative of the viral population significantly increased during the follow-up period. The most resistant pseudotyped virus was identified at the last visit suggesting that it represented a late emerging escape variant. We identified 5 amino acids substitutions that appeared associated with escape to broadly neutralizing antibodies. They were V319I/S, R/K355T, R/W429G, Q460E and G/T463E, in V3, C3 and V5 regions. CONCLUSION: This study showed that HIV-1 may continue to evolve in presence of both broadly neutralizing antibodies and increasing autologous neutralizing activity more than 10 years post-infection

Continuous evolution of HIV-1 more than ten years after infection in an elite neutralizer

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Hypothetical Hypercloso Octahedral M4N2 Clusters: A New Mode of Dinitrogen Coordination?

International audienceDensity functional theory (DFT) calculations carried out on a series of [M4(CO)12N2]2+ and M4(CO)12N2 (M=Fe, Ru, Os) predict that the M4N2 square bipyramidal (octahedral) architecture should be stable for the particular electron count of 6 skeletal electron pairs (or 60 metal valence electrons). This octahedral architecture is electron-deficient with respect to the Wade-Mingos rules and exhibits a through-cage N-N bond of order one. Thus, these hypothetical clusters present a new coordination mode of dinitrogen

Electron-Sponge Behavior, Reactivity and Electronic Structures of Cobalt-Centered Cubic Co9Te6(CO)8 Clusters

International audienceExtended investigations of the reaction sequence [Cp′2Nb(Te2)H]/CH3Li/[Co2(CO)8] (Cp′ = tBuC5H4) led to the identification of Lin[3] {3 = [Co9Te6(CO)8]; n = 1, 2} salts through their transformation with [PPN]Cl into [PPN]n[3] (PPN = Ph3PNPPh3). These compounds form in the solid state columnar ([PPN][3]) or undulated 2D ([PPN]2[3]) supramolecular networks. Electrochemical studies of [Cp*2Nb(CO)2][3] (Cp* = C5Me5) or [Na(THF)6][3] revealed the presence of the redox couples [3]-/[3]2-/[3]3-/[3]4-/[3]5- regardless of the nature of the cation, whereas in the anodic part oxidative degradation of the cluster takes place. This behavior is in agreement with the observation that [3]- containing salts form with PPh3AuCl or dppe decomposition products like [(PPh3)2Au][CoCl3PPh3] or [Co(CO)2dppe]2(μ-Te). A neutral cluster comprising the Co@Co8(μ4-Te)6 core formed in the reaction of [Cp*2Nb(CO)2][Co11Te7(CO)10] with PPh3AuCl, which gave [Co9Te6(CO)4(PPh3)4] (4) after oxidative cluster degradation and CO substitution. 4 was characterized by X-ray crystallography. DFT calculations carried out on all members of the [3]n (n = +1 to -5) family and on related species indicate that there is no significant Jahn-Teller distortion (and therefore no connectivity change) for any of the considered electron counts. Magnetic investigations on [PPN][3] show that the ground state of [3]- is a spin triplet with spins interacting antiferromagnetically in a 1D space

Autologous neutralizing activity of sera from patient 05005.

<p>The autologous neutralizing activity was evaluated toward thirteen pseudoviruses issued from 5 time-points (1997 to 2003). Values correspond to IC₅₀ serum titers. Mean IC₅₀ is indicated for each clone. Mean IC₅₀ and 95% confidence interval (CI 95%) are indicated for each serum.</p

Entropy plot of the 69 <i>env</i> sequences.

<p>Evaluation of the amino-acid variations among the 69 clones over the gp120 envelope. Constant and variable regions are indicated on top. Variable regions are highlighted in light grey. C3 constant region is also highlighted in light grey.</p

Identification of potential amino-acids signature sequence associated with autologous neutralization phenotype in patient 05005.

<p>The sequence includes 5 non-contiguous AA identified as related to autologous Nab activity after pairwise comparison of positively selected amino-acids among thirteen pseudoviruses. Clones are ordered from the most resistant (top) to the least resistant (bottom) in accordance with mean autologous Nab titer. AA associated with sensitivity to autologous neutralization are shown in dark green. AA that differed from the most susceptible but were associated with susceptibility are shown in light green. Conversely, AA associated with resistance to autologous neutralization are shown either in dark red or light red. Numbering positions are relative to HXB2 gp120.</p

Description of the samples and molecular characteristics of the <i>env</i> clones.

<p>dN and dS values result from comparisons between <i>env</i> sequences from a given time-point to sequences from previous one. Mean values and ninety-five percent confidence intervals (CI 95% in brackets) are shown. Estimates of evolutionary divergence over sequence pairs relative to the virus population at enrollment (T0). VL: viral load; cp/mL: copies/mL. Nb AA: number of amino-acids.</p

Cross-neutralizing activity of sera from patient 05005.

<p>Values correspond to IC₅₀. NA: not available. POS: presence of Nab identified previously using a different assay <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044163#pone.0044163-Braibant1" target="_blank">[13]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044163#pone.0044163-Montefiori1" target="_blank">[36]</a>.</p