An integrated genomics approach towards deciphering human genome codes shaping HIV-1 proviral transcription and fate

@article{Ruess2020AnIG,
  title={An integrated genomics approach towards deciphering human genome codes shaping HIV-1 proviral transcription and fate},
  author={H. Ruess and Jeon Lee and Carlos Guzman and V. Malladi and I. D'Orso},
  journal={bioRxiv},
  year={2020}
}
A large body of work has revealed fundamental principles of HIV-1 integration into the human genome. However, the effect of the integration site to proviral transcription activity has so far remained elusive. Here we combine open-source, large-scale datasets including epigenetics, transcriptome, and 3D genome architecture to interrogate the chromatin states, transcription activity landscape, and nuclear sub-compartments around HIV-1 integration sites in CD4+ T cells to decipher human genome… Expand
1 Citations
HIV-1 Proviral Transcription and Latency in the New Era
TLDR
It is proposed that building upon previous discoveries and improved or yet-to-be discovered technologies will unravel molecular mechanisms of latency establishment and reactivation in a “new era”. Expand

References

SHOWING 1-10 OF 63 REFERENCES
Nuclear architecture dictates HIV-1 integration site selection
TLDR
It is shown that HIV-1 integration occurs in the outer shell of the nucleus in close correspondence with the nuclear pore, indicating that nuclear topography is an essential determinant of the HIV- 1 life cycle. Expand
Intact HIV-1 proviruses accumulate at distinct chromosomal positions during prolonged antiretroviral therapy
TLDR
These studies strongly suggest selection of intact proviruses with features of deeper viral latency during prolonged antiretroviral therapy, and may be informative for targeting the genome-intact viral reservoir. Expand
The site of HIV‐1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation
TLDR
It is found that differences in expression levels are due to the integration site and are not controlled by DNA methylation or histone acetylation, and that the HIV Tat protein activates transcription independently of the chromatin environment. Expand
Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 integration
TLDR
It is shown that recurrently targeted genes are proximal to super-enhancer genomic elements, which cluster in specific spatial compartments of the T cell nucleus, suggesting a role for nuclear organisation in viral infection. Expand
HIV latency and integration site placement in five cell-based models
TLDR
The silent/inducible phenotype appears to be associated with chromosomal position, but the molecular basis is not fully clarified and may differ among in vitro models of latency. Expand
Transcriptional interference antagonizes proviral gene expression to promote HIV latency.
TLDR
It is found that viral integration into the actively transcribed host genes led to transcriptional interference (TI) caused by the elongating RNA polymerase II transcribing through the viral promoter, contributing significantly to HIV latency. Expand
HIV Integration Site Analysis of Cellular Models of HIV Latency with a Probe-Enriched Next-Generation Sequencing Assay
TLDR
Findings show that integration site differences exist among the commonly used cellular models of HIV latency and in comparison to integration sites found in patient samples, and a novel probe-based sequence enrichment assay to sequence and analyze integrated HIV is developed. Expand
Physical principles of retroviral integration in the human genome
TLDR
A biophysical model for retroviral integration as stochastic and quasi-equilibrium topological reconnections between polymers is developed, identifying previously unnoticed universal principles that regulate this phenomenon. Expand
Transcriptional control of HIV latency: cellular signaling pathways, epigenetics, happenstance and the hope for a cure.
TLDR
An in-depth comprehensive understanding of the molecular control of HIV-1 transcription should inform the development of optimal combinatorial reactivation strategies that are intended to purge the latent viral reservoir. Expand
HIV-1 Integration in the Human Genome Favors Active Genes and Local Hotspots
TLDR
Global analysis of cellular transcription indicated that active genes were preferential integration targets, particularly genes that were activated in cells after infection by HIV-1, and this data suggests how selective targeting promotes aggressive HIV replication. Expand
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