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Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals

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Abstract
Background: The HIV-1 proviral genome harbors multiple CpG islands (CpGIs), both in the promoter and intragenic regions. DNA methylation in the promoter region has been shown to be heavily involved in HIV-1 latency regulation in cultured cells. However, its exact role in proviral transcriptional regulation in infected individuals is poorly understood or characterized. Moreover, methylation at intragenic CpGIs has never been studied in depth. Results: A large, well-characterized HIV-1 patient cohort (n = 72), consisting of 17 long-term non-progressors and 8 recent seroconverters (SRCV) without combination antiretroviral therapy (cART), 15 early cART-treated, and 32 late cART-treated patients, was analyzed using a next-generation bisulfite sequencing DNA methylation method. In general, we observed low level of promoter methylation and higher levels of intragenic methylation. Additionally, SRCV showed increased promoter methylation and decreased intragenic methylation compared with the other patient groups. This data indicates that increased intragenic methylation could be involved in proviral transcriptional regulation. Conclusions: Contrasting in vitro studies, our results indicate that intragenic hypermethylation of HIV-1 proviral DNA is an underestimated factor in viral control in HIV-1-infected individuals, showing the importance of analyzing the complete proviral genome in future DNA methylation studies.
Keywords
HIV-1, DNA methylation, HIV-1 latency, Epigenetics, Next-generation sequencing, Bisulfite sequencing, Intragenic DNA methylation, T-CELLS, DE-NOVO, CPG, GENE, QUANTIFICATION, REPLICATION, EXPRESSION, ISLANDS, LTR

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MLA
Kint, Sam, et al. “Underestimated Effect of Intragenic HIV-1 DNA Methylation on Viral Transcription in Infected Individuals.” CLINICAL EPIGENETICS, vol. 12, no. 1, 2020, doi:10.1186/s13148-020-00829-1.
APA
Kint, S., Trypsteen, W., De Spiegelaere, W., Malatinková, E., Kinloch-de Loes, S., De Meyer, T., … Vandekerckhove, L. (2020). Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals. CLINICAL EPIGENETICS, 12(1). https://doi.org/10.1186/s13148-020-00829-1
Chicago author-date
Kint, Sam, Wim Trypsteen, Ward De Spiegelaere, Eva Malatinková, Sabine Kinloch-de Loes, Tim De Meyer, Wim Van Criekinge, and Linos Vandekerckhove. 2020. “Underestimated Effect of Intragenic HIV-1 DNA Methylation on Viral Transcription in Infected Individuals.” CLINICAL EPIGENETICS 12 (1). https://doi.org/10.1186/s13148-020-00829-1.
Chicago author-date (all authors)
Kint, Sam, Wim Trypsteen, Ward De Spiegelaere, Eva Malatinková, Sabine Kinloch-de Loes, Tim De Meyer, Wim Van Criekinge, and Linos Vandekerckhove. 2020. “Underestimated Effect of Intragenic HIV-1 DNA Methylation on Viral Transcription in Infected Individuals.” CLINICAL EPIGENETICS 12 (1). doi:10.1186/s13148-020-00829-1.
Vancouver
1.
Kint S, Trypsteen W, De Spiegelaere W, Malatinková E, Kinloch-de Loes S, De Meyer T, et al. Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals. CLINICAL EPIGENETICS. 2020;12(1).
IEEE
[1]
S. Kint et al., “Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals,” CLINICAL EPIGENETICS, vol. 12, no. 1, 2020.
@article{8661643,
  abstract     = {Background: The HIV-1 proviral genome harbors multiple CpG islands (CpGIs), both in the promoter and intragenic regions. DNA methylation in the promoter region has been shown to be heavily involved in HIV-1 latency regulation in cultured cells. However, its exact role in proviral transcriptional regulation in infected individuals is poorly understood or characterized. Moreover, methylation at intragenic CpGIs has never been studied in depth.
Results: A large, well-characterized HIV-1 patient cohort (n = 72), consisting of 17 long-term non-progressors and 8 recent seroconverters (SRCV) without combination antiretroviral therapy (cART), 15 early cART-treated, and 32 late cART-treated patients, was analyzed using a next-generation bisulfite sequencing DNA methylation method. In general, we observed low level of promoter methylation and higher levels of intragenic methylation. Additionally, SRCV showed increased promoter methylation and decreased intragenic methylation compared with the other patient groups. This data indicates that increased intragenic methylation could be involved in proviral transcriptional regulation.
Conclusions: Contrasting in vitro studies, our results indicate that intragenic hypermethylation of HIV-1 proviral DNA is an underestimated factor in viral control in HIV-1-infected individuals, showing the importance of analyzing the complete proviral genome in future DNA methylation studies.},
  articleno    = {36},
  author       = {Kint, Sam and Trypsteen, Wim and De Spiegelaere, Ward and Malatinková, Eva and Kinloch-de Loes, Sabine and De Meyer, Tim and Van Criekinge, Wim and Vandekerckhove, Linos},
  issn         = {1868-7075},
  journal      = {CLINICAL EPIGENETICS},
  keywords     = {HIV-1,DNA methylation,HIV-1 latency,Epigenetics,Next-generation sequencing,Bisulfite sequencing,Intragenic DNA methylation,T-CELLS,DE-NOVO,CPG,GENE,QUANTIFICATION,REPLICATION,EXPRESSION,ISLANDS,LTR},
  language     = {eng},
  number       = {1},
  pages        = {11},
  title        = {Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals},
  url          = {http://dx.doi.org/10.1186/s13148-020-00829-1},
  volume       = {12},
  year         = {2020},
}

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