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Updated: May 8, 2026
10:50
Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
Published on: September 15, 2010
HIV-1 envelope glycoprotein variable loops are indispensable for envelope structural integrity and virus entry.
Tingting Yuan1, Jingjing Li, Mei-Yun Zhang
1AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Plos One
|August 13, 2013
Summary
HIV-1 envelope variable loops are crucial for structural integrity and virus entry. Deleting specific loops like V1-V2, loop D, or V3 abolished entry, while V4/V5 deletions impaired cell surface display and assembly, impacting HIV-1 pathogenesis.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- The human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein, gp160, is essential for viral entry.
- Env is a trimer composed of gp120 and gp41 subunits, with gp120 featuring variable loops (V1-V5) that influence viral properties.
- Variations in these loops are linked to HIV-1 pathogenesis, antibody neutralization sensitivity, and disease progression.
Purpose of the Study:
- To investigate the functional role of each variable loop in the HIV-1 Env glycoprotein.
- To determine how deletions or modifications of variable loops affect Env expression, cell surface display, and virus entry.
Main Methods:
- Generation of a panel of JRFL gp160 loop deletion mutants.
- Assessment of Env expression levels and cell surface display.
- Evaluation of Env-mediated virus entry into permissive cells.
Main Results:
- Deletion of V1-V2, loop D, or V3 abolished virus entry.
- Deletion of the V3 crown enhanced virus assembly and entry.
- Deletion of V4 or V5, or their replacement with linkers, impaired Env cell surface display and virus entry, despite maintaining receptor/coreceptor binding sites.
- V4/V5 deletions exposed the N-trimer and MPER regions of gp41.
Conclusions:
- HIV-1 Env variable loops are indispensable for maintaining Env structural integrity and mediating virus entry.
- These findings highlight the critical role of variable loops in HIV-1 infectivity and may inform the design of vaccine immunogens and therapeutics.
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