Abstract
Human immunodeficiency virus (HIV) is a chronic infection that destroys the immune system in infected individuals. Although antiretroviral therapy is effective at preventing infection of new cells, it is not curative. The inability to clear infection is due to the presence of a rare, but long-lasting latent cellular reservoir. These cells harboring silent integrated proviral genomes have the potential to become activated at any moment, making therapy necessary for life. Latently-infected cells can also proliferate and expand the viral reservoir through several methods including homeostatic proliferation and differentiation. The chromosomal location of HIV proviruses within cells influences the survival and proliferative potential of host cells. Proliferating, latently-infected cells can harbor proviruses that are both replication-competent and defective. Replication-competent proviral genomes contribute to viral rebound in an infected individual. The majority of available techniques can only assess the integration site or the proviral genome, but not both, preventing reliable evaluation of HIV reservoirs.
Highlights
Human immunodeficiency virus (HIV) is a chronic viral infection that causes acquired immunodeficiency syndrome (AIDS) if left untreated
The epigenetic state at the site of viral integration is of great interest for treatments involving histone deacetylase inhibitors (HDI) as they have been proposed as a potential therapeutic option for latency reversal (Figure 4a,b)
Many of the infected cells die from infection, but a small fraction of these cells survives and become quiescent, forming the latent viral reservoir
Summary
Human immunodeficiency virus (HIV) is a chronic viral infection that causes acquired immunodeficiency syndrome (AIDS) if left untreated. Because it is extremely unlikely that any two HIV integration sites are exactly the same, integration site analysis and sequencing of HIV DNA genomes have been used to identify cases in which cellular proliferation is responsible for the production of exact copies of HIV in multiple cells. Each of these methods has their strengths and limitations. CD4+ cell types in the hematopoietic compartment including macrophages and hematopoietic stem cells, each with a different proliferative potential and ability to contribute to maintenance of the latent reservoir [11,12,13,14,15,16]
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