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Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160
R L Willey1, J S Bonifacino, B J Potts
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Abstract:
The synthesis and processing of the human immunodeficiency virus 1 (HIV-1) envelope precursor glycoprotein gp 160 was studied in an infected CD4+ lymphocytic cell line. Surprisingly, only a small percentage (5-15%) of gp160 is cleaved to produce the mature gp120 component. Intracellular sorting results in the transfer of most uncleaved gp160 to lysosomes, where it is degraded, while gp120 is transported to the cell surface and subsequently secreted. Cleavage of gp160 to generate gp120 occurs intracellularly and can be inhibited by NH4Cl. Taken together, these results indicate that intracellular cleavage of gp160 determines the intracellular transport and survival of the envelope glycoproteins necessary to produce infectious virus.
Insights
Most human immunodeficiency virus 1 (HIV-1) envelope precursor glycoprotein gp160 is degraded in lysosomes. Intracellular cleavage of gp160 to gp120 is crucial for viral envelope glycoprotein transport and survival, determining infectious virus production.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- The human immunodeficiency virus 1 (HIV-1) envelope glycoprotein precursor, gp160, is essential for viral entry and infectivity.
- Understanding the intracellular processing and fate of gp160 is critical for developing antiviral strategies.
Purpose of the Study:
- To investigate the synthesis, processing, and intracellular sorting of the HIV-1 envelope precursor glycoprotein gp160.
- To determine the factors influencing the cleavage of gp160 into mature gp120 and its subsequent transport.
Main Methods:
- Studied HIV-1 infected CD4+ lymphocytic cell lines.
- Analyzed intracellular glycoprotein processing and transport pathways.
- Utilized NH4Cl to investigate the inhibition of gp160 cleavage.
Main Results:
- Only a small fraction (5-15%) of gp160 was cleaved to produce gp120.
- The majority of uncleaved gp160 was sorted to lysosomes for degradation.
- Mature gp120 was efficiently transported to the cell surface and secreted.
- Intracellular gp160 cleavage was inhibited by NH4Cl.
Conclusions:
- Intracellular cleavage of gp160 is a key determinant of HIV-1 envelope glycoprotein fate.
- Efficient cleavage is necessary for the transport and survival of envelope glycoproteins required for infectious virus production.
- Lysosomal degradation of uncleaved gp160 impacts viral assembly and infectivity.