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Longitudinal HIV sequencing reveals reservoir expression leading to decay which is obscured by clonal expansion
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019), Nature Communications, Nature communications, 10(1):728. Nature Publishing Group
- Publication Year :
- 2019
- Publisher :
- Nature Portfolio, 2019.
-
Abstract
- After initiating antiretroviral therapy (ART), a rapid decline in HIV viral load is followed by a long period of undetectable viremia. Viral outgrowth assay suggests the reservoir continues to decline slowly. Here, we use full-length sequencing to longitudinally study the proviral landscape of four subjects on ART to investigate the selective pressures influencing the dynamics of the treatment-resistant HIV reservoir. We find intact and defective proviruses that contain genetic elements favoring efficient protein expression decrease over time. Moreover, proviruses that lack these genetic elements, yet contain strong donor splice sequences, increase relatively to other defective proviruses, especially among clones. Our work suggests that HIV expression occurs to a significant extent during ART and results in HIV clearance, but this is obscured by the expansion of proviral clones. Paradoxically, clonal expansion may also be enhanced by HIV expression that leads to splicing between HIV donor splice sites and downstream human exons.<br />How HIV reservoirs are shaped over time on antiviral therapy is poorly understood. Here, the authors analyze the dynamics of the HIV reservoir by longitudinal proviral sequencing revealing that HIV reservoir expression can contribute to its clearance and paradoxically even to its persistence.
- Subjects :
- 0301 basic medicine
Adult
Male
Science
Human immunodeficiency virus (HIV)
Antiretroviral Therapy
General Physics and Astronomy
Viremia
HIV Infections
02 engineering and technology
Biology
medicine.disease_cause
Antiviral Agents
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Exon
Proviruses
Phylogenetics
Antiretroviral Therapy, Highly Active
medicine
Humans
splice
Longitudinal Studies
lcsh:Science
Phylogeny
Mutation
Multidisciplinary
High-Throughput Nucleotide Sequencing
virus diseases
General Chemistry
Middle Aged
Viral Load
021001 nanoscience & nanotechnology
medicine.disease
Virology
3. Good health
Virus Latency
Proviruses, Antiretroviral Therapy, HIV-1
030104 developmental biology
RNA splicing
HIV-1
lcsh:Q
Female
0210 nano-technology
Viral load
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....4cfe3a35fcf260233dd6a13a6b5398be