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Characterization of human immunodeficiency virus type 2 envelope glycoproteins: dimerization of the glycoprotein
M A Rey1, B Krust, A G Laurent
1Unité d'Oncologie Virale (Unité Associée CNRS 1157), Institut Pasteur, Paris, France.
Abstract:
Four glycoproteins with apparent molecular weights of 300,000, 140,000, 125,000, and 36,000 (gp300, gp140, gp125, and gp36) were detectable in human immunodeficiency virus type 2 (HIV-2)-infected cells. gp125 and gp36 are the external and transmembrane components, respectively, of the envelope glycoproteins of HIV-2 mature virions. gp300 and gp140 are only detectable in virus-infected cells. They have identical isoelectric points, suggesting that gp300 might be a dimeric form of the immature precursor, gp140. The purified gp300 can be dissociated in a slightly acidic buffer to give rise to monomers of 140,000 molecular weight. Such dissociated monomers and the purified gp140 showed identical patterns of polypeptides after partial proteolysis with Staphylococcus aureus V8 protease. Pulse-chase experiments indicated that gp300 is formed after synthesis of gp140 and before the detection of the mature external envelope glycoprotein, gp125. These results were confirmed by using various inhibitors of glycosylation and inhibitors of trimming enzymes. Dimer formation of the envelope glycoprotein precursor was also observed in cells infected with simian immunodeficiency virus (SIV), a virus closely related to HIV-2. On the other hand, the envelope glycoprotein precursor of HIV-1 did not form a dimer during its processing. Therefore, dimer formation seems to be a specific property of HIV-2 and SIV envelope gene expression. Such transient dimerization of the glycoprotein precursor might be required for its efficient transport to the Golgi apparatus and for its processing.
Insights
Human immunodeficiency virus type 2 (HIV-2) envelope glycoproteins form transient dimers during processing. This dimerization appears specific to HIV-2 and SIV, potentially aiding transport and maturation.
Area of Science:
- Virology
- Molecular Biology
- Glycoprotein Processing
Background:
- Human immunodeficiency virus type 2 (HIV-2) envelope glycoproteins are crucial for viral entry and assembly.
- Understanding the processing of these glycoproteins is key to understanding viral maturation and potential therapeutic targets.
Purpose of the Study:
- To investigate the processing pathway of HIV-2 envelope glycoproteins.
- To identify specific molecular events, such as dimerization, during HIV-2 glycoprotein maturation.
- To compare HIV-2 glycoprotein processing with that of related viruses like SIV and HIV-1.
Main Methods:
- Detection and characterization of viral glycoproteins in infected cells using molecular weight and isoelectric point analysis.
- Pulse-chase experiments to track glycoprotein synthesis and processing over time.
- Proteolytic digestion (Staphylococcus aureus V8 protease) to compare protein structures.
- Inhibition studies using glycosylation and trimming enzyme inhibitors.
Main Results:
- Four glycoproteins (gp300, gp140, gp125, gp36) were identified in HIV-2 infected cells.
- gp300 was identified as a dimeric form of the immature precursor gp140, dissociating into 140 kDa monomers.
- Dimerization of the envelope glycoprotein precursor was observed in HIV-2 and SIV, but not in HIV-1.
Conclusions:
- Transient dimerization of the envelope glycoprotein precursor is a specific characteristic of HIV-2 and SIV gene expression.
- This dimerization may be essential for efficient transport to the Golgi apparatus and subsequent processing.
- The findings provide insights into the unique maturation pathways of HIV-2 and SIV.