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Rare mutations in a domain crucial for V3-loop structure prevail in replicating HIV from long-term non-progressors
S Menzo1, R Sampaolesi, E Vicenzi
1Istituto di Microbiologia, Università di Ancona, Italy.
AIDS (London, England)
|July 14, 1998
Summary
Host factors shape HIV-1 entry structures, leading to attenuated variants in long-term non-progressors (LTNP). This study reveals how host immune pressure influences viral evolution and infectivity.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- The human immunodeficiency virus type 1 (HIV-1) env gene encodes surface glycoproteins crucial for viral entry.
- The V3 loop of the HIV-1 envelope protein is a key determinant of viral tropism and a target of host immune responses.
Purpose of the Study:
- To investigate the selective pressures exerted by the host on HIV-1 structures involved in viral entry.
- To analyze variations in the V3 loop of HIV-1 in different patient groups.
Main Methods:
- Analysis of V3 loop sequences from cell-free HIV-1 RNA in 17 infected individuals (11 long-term non-progressors and 6 typical progressors).
- Replication of a rare V3 loop variant from a long-term non-progressor into a molecular clone using recombinant PCR for functional evaluation.
Main Results:
- Long-term non-progressors (LTNP) showed distinct V3 loop sequence divergence patterns compared to typical progressors.
- A higher prevalence of unique V3 loop variants with mutations in critical structural domains was observed in LTNP.
- A recombinant HIV-1 mutant with an LTNP-derived V3 loop variant exhibited significantly impaired viral entry and infectivity in cell lines and primary cells.
Conclusions:
- Host factors impose significant selective constraints on the evolution of HIV-1 entry mechanisms.
- These selective pressures may drive the emergence of attenuated HIV-1 variants in long-term non-progressors, contributing to slower disease progression.