更新于：2024-11-01

Envelope glycoprotein gp160 x gp41

更新于：2024-11-01

基本信息

关联

项与 Envelope glycoprotein gp160 x gp41 相关的药物

MB-66

靶点

Envelope glycoprotein gp160 x gp41

作用机制

包膜糖蛋白gp160抑制剂 [+1]

在研机构

Mapp Biopharmaceutical, Inc.

原研机构

Mapp Biopharmaceutical, Inc.

在研适应症

单纯疱疹 [+1]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 Envelope glycoprotein gp160 x gp41 相关的临床结果

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100 项与 Envelope glycoprotein gp160 x gp41 相关的转化医学

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0 项与 Envelope glycoprotein gp160 x gp41 相关的专利（医药）

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项与 Envelope glycoprotein gp160 x gp41 相关的文献（医药）

2014-03-01·Journal of Virology2区 · 医学

Enhanced Central Nervous System Transduction with Lentiviral Vectors Pseudotyped with RVG/HIV-1gp41 Chimeric Envelope Glycoproteins

2区 · 医学

Article

作者: Mazarakis, Nicholas D. ; Liao, Ting-Yi ; Patsali, Petros ; Eleftheriadou, Ioanna ; Sgourou, Argyro ; Lee, Heyne ; Trabalza, Antonio

ABSTRACT To investigate the potential benefits which may arise from pseudotyping the HIV-1 lentiviral vector with its homologous gp41 envelope glycoprotein (GP) cytoplasmic tail (CT), we created chimeric RVG/HIV-1gp41 GPs composed of the extracellular and transmembrane sequences of RVG and either the full-length gp41 CT or C terminus gp41 truncations sequentially removing existing conserved motifs. Lentiviruses (LVs) pseudotyped with the chimeric GPs were evaluated in terms of particle release (physical titer), biological titers, infectivity, and in vivo central nervous system (CNS) transduction. We report here that LVs carrying shorter CTs expressed higher levels of envelope GP and showed a higher average infectivity than those bearing full-length GPs. Interestingly, complete removal of GP CT led to vectors with the highest transduction efficiency. Removal of all C-terminal gp41 CT conserved motifs, leaving just 17 amino acids (aa), appeared to preserve infectivity and resulted in a significantly increased physical titer. Furthermore, incorporation of these 17 aa in the RVG CT notably enhanced the physical titer. In vivo stereotaxic delivery of LV vectors exhibiting the best in vitro titers into rodent striatum facilitated efficient transduction of the CNS at the site of injection. A particular observation was the improved retrograde transduction of neurons in connected distal sites that resulted from the chimeric envelope R5 which included the “Kennedy” sequence (Ken) and lentivirus lytic peptide 2 (LLP2) conserved motifs in the CT, and although it did not exhibit a comparable high titer upon pseudotyping, it led to a significant increase in distal retrograde transduction of neurons. IMPORTANCE In this study, we have produced novel chimeric envelopes bearing the extracellular domain of rabies fused to the cytoplasmic tail (CT) of gp41 and pseudotyped lentiviral vectors with them. Here we report novel effects on the transduction efficiency and physical titer of these vectors, depending on CT length and context. We also managed to achieve increased neuronal transduction in vivo in the rodent CNS, thus demonstrating that the efficiency of these vectors can be enhanced following merely CT manipulation. We believe that this paper is a novel contribution to the field and opens the way for further attempts to surface engineer lentiviral vectors and make them more amenable for applications in human disease.

1995-08-01·Archives of Virology4区 · 医学

Endoproteolytic cleavage of HIV-1 gp160 envelope precursor occurs after exit from the trans-Golgi network (TGN)

4区 · 医学

Article

作者: P. Leinikki ; M. L. Kantanen ; E. Kuismanen

Endoproteolytic processing of human immunodeficiency virus type 1 (HIV-1) gp160 membrane glycoprotein precursor into gp 120 and gp41 is necessary for formation of infectious HIV particles [1]. We have studied the intracellular site of this processing using inhibition of transport at reduced temperature (20 degrees C). That reduced temperature (20 degrees C) inhibits the intracellular transport also in Jurkat-tat cells was demonstrated using the Semliki Forest virus p62 precursor processing as model. In HIV-1 infected Jurkat-tat cells the proteolytic processing of gp 160 precursor did not occur when the protein was accumulated in the TGN at 20 degrees C temperature. When the temperature was shifted to 37 degrees C the HIV-1 gp 160, which had accumulated in the TGN at the reduced temperature, was proteolytically processed. The processing of gp 160 was inhibited when the temperature reversion was carried out in the presence of brefeldin A (BFA) or aluminium fluoride (ALFn) indicating that the exit from the TGN is required for the proteolytic cleavage of HIV-1 gp160 precursor. The results suggest that the processing of gp 160 takes place at a yet unidentified transport step which is distal to the TGN/20 degrees C block site.

1994-10-01·European Journal of Biochemistry

Kex2p: a model for cellular endoprotease processing human immunodeficiency virus type 1 envelope glycoprotein precursor

Article

作者: Elmostafa Bahraoui ; Luc Montagnier ; Marie-Paule Kieny ; Maxime Moulard ; Tilman Achstetter

The endoproteolytic cleavage of the envelope glycoprotein precursor (gp160) of the human immunodeficiency virus type 1 (HIV‐1) by a cellular protease is required for full activation of the virus. In this study, processing of gp160 was analyzed in vitro using the Kex2p endoprotease from the yeast Saccharomyces cerevisiae as a processing enzyme model. Endoproteolytic processing was examined using a synthetic peptide that mimics the cleavage site of HIV‐1 glycoprotein, and a recombinant gp160 bearing the entire sequence of the env gene product, including the conserved cleavage site Arg508‐Glu‐Lys‐Arg511. Coexpression in BHK‐21 of Kex2p and gp160 by recombinant vaccinia viruses demonstrates that Kex2p can correctly process the HIV‐1 glycoprotein to gp120 and gp41. Furthermore, recombinant gp160 and peptide were used as substrates and subjected to proteolysis with purified membranes from an S. cerevisiae strain overproducing the Kex2p endoprotease. Treatment of recombinant gp160, which has an apparent molecular mass of 127 kDa, with Kex2p and Western blot analysis showed that the precursor was cleaved into two products of about 101 and 34 kDa apparent molecular mass. Amino acid sequencing of the NH2‐terminus of the 34‐kDa product showed that the cleavage site of recombinant gp160 was between Arg511 and Ala512. Recombinant gp160 mutated at the sequence coding for the potential cleavage site, and mature recombinant gp120, however, were not cleaved when treated with Kex2p. In summary, our results show that Kex2p cleaves both the HIV‐1 envelope glycoprotein precursor and a synthetic peptide mimicking the cleavage site of HIV‐1 gp160 at the dibasic site, suggesting functional analogy between yeast Kex2p and the cellular protease responsible for the maturation of HIV‐1 envelope glycoproteins in infected human cells.