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Updated: Dec 10, 2025

A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses

Published on: August 31, 2014

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Infection with multiple HIV-1 founder variants is associated with lower viral replicative capacity, faster CD4+ T

Gladys N Macharia1,2, Ling Yue3, Ecco Staller1,2

  • 1Department of Medicine, Imperial College London, London, United Kingdom.

Plos Pathogens
|September 4, 2020
PubMed

Insights

Multivariant HIV-1 infection, common in men who have sex with men (MSM), is linked to lower gag replicative capacity and faster CD4+ T cell decline. Strategies to reduce multiple variant infections may improve HIV-1 prognosis and aid vaccine development.

Area of Science:

  • Virology
  • Immunology
  • Epidemiology

Background:

  • HIV-1 transmission involves a genetic bottleneck, with limited variants establishing infection.
  • The IAVI Protocol C cohort provides a unique opportunity to study transmitted/founder (TF) viruses in diverse risk groups.

Purpose of the Study:

  • To characterize transmitted/founder (TF) HIV-1 viruses in men who have sex with men (MSM).
  • To assess the impact of multivariant infection on viral replicative capacity and disease progression.
  • To evaluate the role of TF viruses in predicting disease outcome and immune response.

Main Methods:

  • Sequencing of HIV-1 repertoire in MSM participants near transmission.
  • Generation and characterization of chimeric viruses using patient-derived gag genes.
  • Evaluation of TF virus impact on disease progression and immune responses.

Main Results:

  • Higher prevalence of multivariant HIV-1 infection observed in MSM compared to heterosexual cohorts.
  • Multivariant infection associated with lower replicative capacity of TF gag genes (p = 0.02).
  • Multivariant infection linked to rapid CD4+ T cell decline and immune cell disturbances, reversible upon viremia control.

Conclusions:

  • Multivariant infection in MSM impacts viral fitness and accelerates disease progression.
  • Strategies to tighten the transmission bottleneck, like STI treatment, could improve HIV-1 prognosis.
  • TF sequences and chimeric viruses are valuable for vaccine immunogen design and immune response studies.

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