Proteomics computational analyses suggest that the bornavirus glycoprotein is a class III viral fusion protein (γ penetrene)

Abstract Background Borna disease virus (BDV) is the type member of the Bornaviridae, a family of viruses that induce often fatal neurological diseases in horses, sheep and other animals, and have been proposed to have roles in certain psychiatric diseases of humans. The BDV glycoprotein (G) is an extensively glycosylated protein that migrates with an apparent molecular mass of 84,000 to 94,000 kilodaltons (kDa). BDV G is post-translationally cleaved by the cellular subtilisin-like protease furin into two subunits, a 41 kDa amino terminal protein GP1 and a 43 kDa carboxyl terminal protein GP2. Results Class III viral fusion proteins (VFP) encoded by members of the Rhabdoviridae, Herpesviridae and Baculoviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Proteomics computational analyses suggest that the structural/functional motifs that characterize class III VFP are located collinearly in BDV G. Structural models were established for BDV G based on the post-fusion structure of a prototypic class III VFP, vesicular stomatitis virus glycoprotein (VSV G). Conclusion These results suggest that G encoded by members of the Bornavirdae are class III VFPs (gamma-penetrenes).</p

Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits

Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design

Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes

Courtney E. Garry is with the Department of Biology, The University of Texas at Austin, Austin, Texas, 78701, USA -- Robert F. Garry is with the Department of Microbiology and Immunology, Tulane University Heath Sciences Center, New Orleans, Louisiana, 70112, USABackground: Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV) form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP) encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. -- Results: Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G), were established for Thogoto virus (THOV) GP and Autographa california multiple NPV (AcMNPV) GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. -- Conclusion: These results suggest that proteins in the GP64 superfamily are class III penetrenes.Molecular [email protected]

The predicted structures of THOV GP and AcMNPV GP64 were fit to the post-fusion structure of VSV G 17

Secondary structures for THOV GP and AcMNPV GP64 were predicted by PHD or by alignment to VSV G. The structure of HSV-1 gB [19] is shown for comparison. Domain coloring as in Fig. 1 and Fig. 2A. Orange/black lines: dicysteine linkages as in Fig. 2. Black stick figures: N-glycosylation sites.<p><b>Copyright information:</b></p><p>Taken from "Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes"</p><p>http://www.virologyj.com/content/5/1/28</p><p>Virology Journal 2008;5():28-28.</p><p>Published online 18 Feb 2008</p><p>PMCID:PMC2288602.</p><p></p

Alignment of HE2 of influenza C virus with HA2 of influenza A and B virus and Fof ISAV

Fusion peptide red, amino terminal helix (N-helix) orange, c-terminal helix (green), aromatic domain (indigo). Hydrophobic transmembrane domains (violet).<p><b>Copyright information:</b></p><p>Taken from "Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes"</p><p>http://www.virologyj.com/content/5/1/28</p><p>Virology Journal 2008;5():28-28.</p><p>Published online 18 Feb 2008</p><p>PMCID:PMC2288602.</p><p></p

A common domain nomenclature for class III penetrenes is utilized: domain I (green), domain II (yellow), domain III (blue), and stem domain (indigo)

The domain numbering originally proposed is also indicated [17]. UA represents "hinge" aa not assigned to domains in VSV G in the prior scheme. Sequences with significant WWIHS scores in the fusion domain (II) were identified by MPeX and colored red. Hydrophobic transmembrane domains (violet) were predicted using TMpred. The post fusion secondary structure of VSV G as solved and numbered by Roche and coworkers [17] is depicted with α-helices as cylinders and β-sheets as arrows. The α-helices predicted by PHD In THOV GP and AcMNPV GP64 are indicated similarly. β-sheets (t) and (u) of VSV G are not present in the protein data base structure (2cmz.pdb). In VSV G, α-helices predicted by PHD are indicated by dashed boxes and predicted β-sheets are identified with dashed arrows. Amino acids are numbered beginning after the putative signal sequences enclosed in parentheses. In the alignments (:) refers to identical amino acids. (.) refers to chemically similar amino acids. Plum amino acids: N-glycosylation sites.<p><b>Copyright information:</b></p><p>Taken from "Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes"</p><p>http://www.virologyj.com/content/5/1/28</p><p>Virology Journal 2008;5():28-28.</p><p>Published online 18 Feb 2008</p><p>PMCID:PMC2288602.</p><p></p

Amino acids are numbered beginning after the putative signal sequences in VSV G, but at the beginning of the signal sequence of HSV-1 gB

Arrows indicate G and gB truncations of the forms used for crystallography. Solid lines represent cysteine bonding in VSV G and HSV-1 gB. Black boxes represent hydrophobic regions, with violet representing the transmembrane anchor (TM) [51]. Dashed lines represent potential cysteine bonding in THOV GP and AcMNPV GP64. Panel A: class III penetrene domain nomenclature and coloring as in Fig. 1. Panel B: domain nomenclature and color coding schemes used previously for VSV G [17] and for HSV-1 gB [19]. Hatched boxes in VSV G represent "hinge" aa not assigned to domains.<p><b>Copyright information:</b></p><p>Taken from "Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes"</p><p>http://www.virologyj.com/content/5/1/28</p><p>Virology Journal 2008;5():28-28.</p><p>Published online 18 Feb 2008</p><p>PMCID:PMC2288602.</p><p></p