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Updated: Dec 9, 2025
Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
Published on: September 14, 2014
Differential utilization of CD4+ by transmitted/founder and chronic envelope glycoproteins in a MSM HIV-1 subtype B
Mélanie Bouvin-Pley1, Marie Leoz2, Emmanuelle Roch1
1INSERM U1259, Université de Tours et CHRU de Tours, Tours.
Objective:
HIV-1 transmission leads to a genetic bottleneck, with one or a few variants of the donor quasispecies establishing an infection in the new host. We aimed to characterize this bottleneck in more detail, by comparing the properties of HIV envelope glycoproteins from acute and chronic infections within the particular context of a male-to-male transmission cluster.
Design:
We compared the genotypic and phenotypic properties of envelope glycoproteins from viral variants derived from five study participants from the same transmission cluster.
Methods:
We used single-genome amplification to generate a collection of full-length env sequences. We then constructed pseudotyped viruses expressing selected Env variants from the quasispecies infecting each study participant and compared their infectivities and sensitivities to various entry inhibitors.
Results:
The genotypic analyses confirmed the genetic bottleneck expected after HIV transmission, with a limited number of variants identified in four study participants during acute infection. However, the transmitted sequences harbored no evident common signature and belonged to various genetic lineages. The phenotypic analyses revealed no difference in infectivity, susceptibility to the CCR5 antagonist maraviroc, the fusion inhibitor enfurvitide or type-I interferon between viruses from participants with acute and chronic infections. The key property distinguishing transmitted viruses was a higher resistance to soluble CD4, correlated with greater sensitivity to occupation of the CD4 receptor by the anti-CD4 antibodies LM52 and SK3.
Conclusion:
These results suggest that envelope glycoproteins from transmitted/founder viruses bind CD4 less efficiently than those of viruses from chronic infections.
Insights
The genetic bottleneck in HIV-1 transmission involves limited viral variants. Transmitted HIV envelope glycoproteins bind CD4 less efficiently than those in chronic infections, impacting early viral entry.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- HIV-1 transmission typically results in a genetic bottleneck, where only a few donor viral variants establish infection.
- Understanding the characteristics of these transmitted viral strains is crucial for comprehending early HIV infection dynamics.
Purpose of the Study:
- To characterize the genetic and phenotypic properties of HIV envelope glycoproteins during acute and chronic infections within a male-to-male transmission cluster.
- To detail the genetic bottleneck by comparing viral variants from early and later stages of infection.
Main Methods:
- Single-genome amplification was used to obtain full-length env sequences from infected participants.
- Pseudotyped viruses expressing selected Env variants were constructed to assess infectivity and sensitivity to entry inhibitors.
Main Results:
- Genotypic analysis confirmed a genetic bottleneck in acute infections, with limited variants, but no common signature was observed.
- Phenotypic analysis showed no significant differences in infectivity or susceptibility to maraviroc, enfuvirtide, or interferon between acute and chronic infection viruses.
- Transmitted viruses exhibited higher resistance to soluble CD4, correlating with increased sensitivity to anti-CD4 antibodies.
Conclusions:
- HIV envelope glycoproteins from transmitted/founder viruses demonstrate less efficient binding to CD4 compared to viruses from chronic infections.
- This altered CD4 binding property may be a key characteristic of early transmitted HIV strains.
