TY - JOUR
T1 - Epigenetic analysis of HIV-1 proviral genomes from infected individuals
T2 - Predominance of unmethylated CpG's
AU - Weber, Stefanie
AU - Weiser, Barbara
AU - Kemal, Kimdar S.
AU - Burger, Harold
AU - Ramirez, Christina M.
AU - Korn, Klaus
AU - Anastos, Kathryn
AU - Kaul, Rupert
AU - Kovacs, Colin
AU - Doerfler, Walter
N1 - Funding Information:
We are indebted to J. Hildreth and F. Chedin at UC Davis for helpful scientific discussions, and we thank the Wadsworth Center Forensic Identity Program for performing the forensic analysis. We thank the study subjects for their participation. We thank our colleagues in the sequencing facility of the Institute for Human Genetics, Erlangen University for sequencing work and Grit Schneider, Erlangen, for assistance with the DNA extraction control. This investigation was supported by the Deutsche Forschungsgemeinschaft, Bonn, Germany DO 165/28-1 ; US National Institutes of Health grant UO1-AI 35004 ; Canadian Institutes of Health Research grant HET-85518 ; and by the Institute for Virology, Erlangen University .
PY - 2014/1/20
Y1 - 2014/1/20
N2 - Efforts to cure HIV-1 infections aim at eliminating proviral DNA. Integrated DNA from various viruses often becomes methylated de novo and transcriptionally inactivated. We therefore investigated CpG methylation profiles of 55 of 94 CpG's (58.5%) in HIV-1 proviral genomes including ten CpG's in each LTR and additional CpG's in portions of gag, env, nef, rev, and tat genes. We analyzed 33 DNA samples from PBMC's of 23 subjects representing a broad spectrum of HIV-1 disease. In 22 of 23 HIV-1-infected individuals, there were only unmethylated CpG's regardless of infection status. In one long term nonprogressor, however, methylation of proviral DNA varied between 0 and 75% over an 11-year period although the CD4+ counts remained stable. Hence levels of proviral DNA methylation can fluctuate. The preponderance of unmethylated CpG's suggests that proviral methylation is not a major factor in regulating HIV-1 proviral activity in PBMC's. Unmethylated CpG's may play a role in HIV-1 immunopathogenesis.
AB - Efforts to cure HIV-1 infections aim at eliminating proviral DNA. Integrated DNA from various viruses often becomes methylated de novo and transcriptionally inactivated. We therefore investigated CpG methylation profiles of 55 of 94 CpG's (58.5%) in HIV-1 proviral genomes including ten CpG's in each LTR and additional CpG's in portions of gag, env, nef, rev, and tat genes. We analyzed 33 DNA samples from PBMC's of 23 subjects representing a broad spectrum of HIV-1 disease. In 22 of 23 HIV-1-infected individuals, there were only unmethylated CpG's regardless of infection status. In one long term nonprogressor, however, methylation of proviral DNA varied between 0 and 75% over an 11-year period although the CD4+ counts remained stable. Hence levels of proviral DNA methylation can fluctuate. The preponderance of unmethylated CpG's suggests that proviral methylation is not a major factor in regulating HIV-1 proviral activity in PBMC's. Unmethylated CpG's may play a role in HIV-1 immunopathogenesis.
KW - Bisulfite sequencing
KW - Epigenetics of HIV-1 proviral DNA
KW - Escape from proviral DNA methylation
KW - Fluctuation of CpG methylation in one LTNP individual
KW - Integrated HIV-1 DNA in PBMC's from infected individuals
KW - Methylation analysis of integrated HIV-1 genomes
KW - Predominance of unmethylated CpG's in PBMC's
KW - Wide spectrum of infection outcome
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U2 - 10.1016/j.virol.2013.11.013
DO - 10.1016/j.virol.2013.11.013
M3 - Article
C2 - 24418551
AN - SCOPUS:84890290379
SN - 0042-6822
VL - 449
SP - 181
EP - 189
JO - Virology
JF - Virology
ER -