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Updated: Jun 28, 2026
07:10
Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
Published on: January 7, 2019
HIV rebounds from latently infected cells, rather than from continuing low-level replication
Beda Joos1, Marek Fischer, Herbert Kuster
1Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, CH-8091 Zurich, Switzerland. beda.joos@usz.ch
Summary
HIV rebound after combination antiretroviral therapy (cART) interruption stems from reactivated latent cells, not low-level replication. This suggests a sustained evolutionary bottleneck, delaying viral diversity restoration post-treatment.
Area of Science:
- Virology
- Immunology
- Evolutionary Biology
Background:
- Long-term combination antiretroviral therapy (cART) suppresses HIV-1 replication.
- Interruption of cART leads to rapid viral rebound, suggesting persistent reservoirs or reactivation.
Purpose of the Study:
- To investigate the origin and evolution of rebounding HIV during structured treatment interruptions (STI).
- To determine if low-level replication or reactivation of latent cells drives viral rebound.
Main Methods:
- Longitudinal clonal evolutionary studies of HIV env C2-V3-C3 regions.
- Analysis of rebounding plasma viruses in 20 HIV-1 patients during multiple 2-week STIs.
- Comparison of rebounding virus sequences with pretreatment sequences.
Main Results:
- Rebounding virus during STI was homogeneous, indicating mono- or oligoclonal origin.
- No temporal structure found between rebounding virus and pretreatment sequences.
- Distinct viral lineages emerged at different STI cycles, implying stochastic reactivation from latent reservoirs.
- Restoration of pretreatment viral diversity took over 2.5 years, revealing a sustained evolutionary bottleneck.
Conclusions:
- HIV rebound after cART interruption is driven by stochastic reactivation of latent clones, not ongoing low-level replication.
- Punctuated antiretroviral therapy induces a prolonged evolutionary bottleneck, delaying viral diversity recovery.
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