Suboptimal provirus expression explains apparent nonrandom cell coinfection with HIV-1
Christelle Brégnard1, Gregory Pacini, Olivier Danos
1Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Journal of Virology
|June 15, 2012
Summary
Cell coinfection with human immunodeficiency virus (HIV) is more common than random, driven by silent proviruses reactivated during coinfection. This interaction influences viral evolution and depends on cell type but not entry route.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Primate lentiviruses, including human immunodeficiency virus (HIV), possess mechanisms to prevent reinfection of already infected cells.
- Despite this, cell coinfection has been observed and is crucial in shaping viral evolution through mechanisms like recombination.
- Previous in vitro studies suggest HIV coinfection occurs more frequently than predicted by random chance, possibly due to target cell heterogeneity.
Purpose of the Study:
- To investigate the mechanisms underlying the non-random frequency of HIV cell coinfection.
- To determine if silent proviruses and viral cross-talk contribute to the observed coinfection bias.
- To assess the influence of cell type and virus entry route on coinfection dynamics.
Main Methods:
- Coincubation of cells with two distinct HIV reporter viruses (GFP and DsRed) to quantify double-positive cells.
- Comparison of experimentally determined coinfection frequencies with calculated stochastic coinfection rates.
- Analysis of viral cross-talk and silent provirus reactivation by controlling for these factors.
Main Results:
- Observed coinfection frequencies were higher than predicted by stochastic models, primarily due to underestimation of single-infection rates.
- A significant fraction of cells initially appearing uninfected harbored a silent provirus, which could be reactivated upon coinfection via viral cross-talk.
- When viral cross-talk was mitigated, experimental and calculated coinfection frequencies aligned, indicating random coinfection.
- The prevalence of cells with silent proviruses was dependent on cell type but not on the virus entry route.
Conclusions:
- HIV cell coinfection is not a purely random process and is influenced by the presence and reactivation of silent proviruses.
- Viral cross-talk between elements of different viruses plays a key role in the observed non-random coinfection patterns.
- Understanding these mechanisms is vital for comprehending HIV evolution and pathogenesis, with implications for therapeutic strategies.
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