Peptide P5 (residues 628–683), comprising the entire membrane proximal region of HIV-1 gp41 and its calcium-binding site, is a potent inhibitor of HIV-1 infection

The membrane proximal region (MPR) of the transmembrane subunit, gp41, of the HIV envelope glycoprotein plays a critical role in HIV-1 infection of CD4+ target cells and CD4-independent mucosal entry. It contains continuous epitopes recognized by neutralizing IgG antibodies 2F5, 4E10 and Z13, and is therefore considered to be a promising target for vaccine design. Moreover, some MPR-derived peptides, such as T20 (enfuvirtide), are in clinical use as HIV-1 inhibitors. We have shown that an extended MPR peptide, P5, harbouring the lectin-like domain of gp41 and a calcium-binding site, is implicated in the interaction of HIV with its mucosal receptor. We now investigate the potential antiviral activities of P5 and other such long MPR-derived peptides. Structural studies of gp41 MPR-derived peptides using circular dichroism showed that the peptides P5 (a.a.628–683), P1 (a.a.648–683), P5L (a.a.613–683) and P7 (a.a.613–746) displayed a well-defined α-helical structure. Peptides P5 inhibited HIV-1 envelope mediated cell-cell fusion and infection of peripheral blood mononuclear cells by both X4- and R5-tropic HIV-1 strains, whereas peptides P5 mutated in the calcium binding site or P1 lacked antiviral activity, when P5L blocked cell fusion in contrast to P7. Strikingly, P5 inhibited CD4-dependent infection by T20-resistant R5-tropic HIV-1 variants. Cell-cell fusion studies indicated that the anti-HIV-1 activity of P5, unlike T20, could not be abrogated in the presence of the N-terminal leucine zipper domain (LZ). These results suggested that P5 could serve as a potent fusion inhibitor

The venom composition of the parasitic wasp Chelonus inanitus resolved by combined expressed sequence tags analysis and proteomic approach

<p>Abstract</p> <p>Background</p> <p>Parasitic wasps constitute one of the largest group of venomous animals. Although some physiological effects of their venoms are well documented, relatively little is known at the molecular level on the protein composition of these secretions. To identify the majority of the venom proteins of the endoparasitoid wasp <it>Chelonus inanitus </it>(Hymenoptera: Braconidae), we have randomly sequenced 2111 expressed sequence tags (ESTs) from a cDNA library of venom gland. In parallel, proteins from pure venom were separated by gel electrophoresis and individually submitted to a nano-LC-MS/MS analysis allowing comparison of peptides and ESTs sequences.</p> <p>Results</p> <p>About 60% of sequenced ESTs encoded proteins whose presence in venom was attested by mass spectrometry. Most of the remaining ESTs corresponded to gene products likely involved in the transcriptional and translational machinery of venom gland cells. In addition, a small number of transcripts were found to encode proteins that share sequence similarity with well-known venom constituents of social hymenopteran species, such as hyaluronidase-like proteins and an Allergen-5 protein.</p> <p>An overall number of 29 venom proteins could be identified through the combination of ESTs sequencing and proteomic analyses. The most highly redundant set of ESTs encoded a protein that shared sequence similarity with a venom protein of unknown function potentially specific of the <it>Chelonus </it>lineage. Venom components specific to <it>C. inanitus </it>included a C-type lectin domain containing protein, a chemosensory protein-like protein, a protein related to yellow-e3 and ten new proteins which shared no significant sequence similarity with known sequences. In addition, several venom proteins potentially able to interact with chitin were also identified including a chitinase, an imaginal disc growth factor-like protein and two putative mucin-like peritrophins.</p> <p>Conclusions</p> <p>The use of the combined approaches has allowed to discriminate between cellular and truly venom proteins. The venom of <it>C. inanitus </it>appears as a mixture of conserved venom components and of potentially lineage-specific proteins. These new molecular data enrich our knowledge on parasitoid venoms and more generally, might contribute to a better understanding of the evolution and functional diversity of venom proteins within Hymenoptera.</p

ROLE DES GLYCOPROTEINES D'ENVELOPPE DES VIRUS DE L'IMMUNODEFICIENCE HUMAINE DE TYPE 1 DANS L'ENTREE VIRALE (ETUDE DU MECANISME D'ACTION DE DEUX ANTIVIRAUX)

PARIS-BIUSJ-Physique recherche (751052113) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

WHO collaborative study to assess the suitability of an interim standard for antibodies to Ebola virus

In support of the WHO response to the Ebola crisis, NIBSC is undertaking a project to develop an International Standard for use in the calibration and control of Ebola antibody assays. The availability of International Standards (IS) for antibodies would facilitate the standardization of Ebola serological methods used in epidemiological studies to measure past or present Ebola virus disease and in vaccinology studies to measure antibodies elicited by vaccination in humans. In the absence of such standards, individual laboratories apply their own reference standards which are not harmonized with other laboratories and methods and thus cannot serve to improve the reproducibility between laboratories. Recommendations made by participants attending the Technical Workshop on the Standardisation of Serological and PCR assays for the detection of Ebola virus (NIBSC, UK, 5-6 March 2015), included the urgent prioritization of the development of an interim Ebola standard for serology assays while perusing the longer-term goal of establishing an International Standard according to published WHO guidelines and formally endorsed by the WHO Expert Committee on Biological Standardization (ECBS). This report describes the development and worldwide collaborative study evaluation of a panel of candidate Ebola antibody preparations for the selection of the most appropriate candidate to serve as the interim WHO standard for Ebola antibody assays