scholarly journals Structural characterization of the feline-immunodeficiency-virus envelope glycoprotein 36 ectodomain for the development of new antivirals

2005 ◽  
Vol 389 (2) ◽  
pp. 559-567 ◽  
Author(s):  
Florestan Desmaris ◽  
David Lemaire ◽  
Sylvie Ricard-Blum ◽  
Benoît Chatrenet ◽  
Eric Forest

In the fight against the human HIV, new targets are being explored, such as the proteins involved in the process of fusion of the virus with the host cell. Recently, the first generation of fusion inhibitors (enfuvirtide), targeting gp41 (virus envelope glycoprotein 41), has become commercially available. However, this promising class of drugs has to be improved in respect of their efficacy and bioavailability. Considering the strong homologies between HIV and FIV (feline immunodeficiency virus), as well as the highly conserved structure of the transmembrane envelope protein among species, FIV represents a relevant model of pre-screening studies for HIV. Taking into account (i) sequence homologies between the ectodomain of HIV gp41 and FIV gp36 (envelope glycoprotein 36), (ii) structural data available for gp41 and (iii) the fact that synthetic peptides derived from gp36 are effective inhibitors of FIV infection, we designed several peptides derived from gp36 sequence. We checked that these peptides had the same structural features as the corresponding peptides from gp41 HIV by CD, analytical ultracentrifugation and 1H–2H (hydrogen–deuterium) exchange combined with MS. By combining this latter technique with surface-plasmon-resonance assays, we identified the amino acid residues of the C-terminal region of the ectodomain of gp36 that are critical for interaction with the N-terminal region. This gave clues for therapy and vaccines against FIV, thus providing helpful data for treatments against HIV.

2012 ◽  
Vol 86 (12) ◽  
pp. 6688-6700 ◽  
Author(s):  
M. Celestino ◽  
A. Calistri ◽  
C. Del Vecchio ◽  
C. Salata ◽  
F. Chiuppesi ◽  
...  

2004 ◽  
Vol 78 (9) ◽  
pp. 4921-4926 ◽  
Author(s):  
Joanne York ◽  
Jack H. Nunberg

ABSTRACT The interaction between the gp120 and gp41 subunits of the human immunodeficiency virus envelope glycoprotein serves to stabilize the virion form of the complex and to transmit receptor-induced conformational changes in gp120 to trigger the membrane fusion activity of gp41. In this study, we used site-directed mutagenesis to identify amino acid residues in the central ectodomain of gp41 that contribute to the stability of the gp120-gp41 association. We identified alanine mutations at six positions, including four tryptophan residues, which result in mutant envelope glycoprotein complexes that fail to retain gp120 on the cell surface. These envelope glycoproteins readily shed their gp120 and are unable to mediate cell-cell fusion. These findings suggest an important role for the conserved bulky hydrophobic residues in stabilizing the gp120-gp41 complex.


Virology ◽  
2004 ◽  
Vol 321 (2) ◽  
pp. 274-286 ◽  
Author(s):  
Himanshu Garg ◽  
Frederick J. Fuller ◽  
Wayne A.F. Tompkins

2004 ◽  
Vol 85 (7) ◽  
pp. 1833-1841 ◽  
Author(s):  
Willem Huisman ◽  
Eefje J. A. Schrauwen ◽  
Suzan D. Pas ◽  
Jos A. Karlas ◽  
Guus F. Rimmelzwaan ◽  
...  

In a previous vaccination study in cats, the authors reported on accelerated feline immunodeficiency virus (FIV) replication upon challenge in animals vaccinated with a candidate envelope subunit vaccine. Plasma transfer studies as well as antibody profiles in vaccinated cats indicated a causative role for antibodies directed against the hypervariable regions HV3, HV4 and HV5 (HV3–5) of the envelope glycoprotein. The present study was designed to investigate further the contribution of antibodies in envelope vaccine-induced acceleration of FIV infection. To this end, regions HV3–5 of the envelope glycoprotein were deleted from the original vaccine, thus addressing the contributing role of antibodies directed against these hypervariable regions. Interestingly, this approach did not prevent acceleration of challenge infection. Analysis of the antibody responses in the respective groups suggested that removal of HV3–5 redirected the humoral immune response towards other regions of the envelope glycoprotein, indicating that these regions can also induce antibodies that accelerate virus replication.


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