title: Epigenetic analysis of HIV-1 proviral genomes from infected individuals: predominance of unmethylated CpG's.
abstract: 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.
authors.affiliation: Institute for Clinical and Molecular Virology, Erlangen University Medical School, Schlossgarten 4, D-91054 Erlangen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Weber
authors.affiliation: University of California, Davis School of Medicine and Sacramento Veterans Administration Medical Center, Sacramento, CA 95655, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Weiser
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Kimdar S
authors.initials: KS
authors.lastname: Kemal
authors.affiliation: University of California, Davis School of Medicine and Sacramento Veterans Administration Medical Center, Sacramento, CA 95655, USA.
authors.forename: Harold
authors.initials: H
authors.lastname: Burger
authors.affiliation: University of California, Los Angeles, CA 90095, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Ramirez
authors.affiliation: Institute for Clinical and Molecular Virology, Erlangen University Medical School, Schlossgarten 4, D-91054 Erlangen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Korn
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.affiliation: University of Toronto, Toronto, ON, Canada M55 1A8.
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.affiliation: University of Toronto, Toronto, ON, Canada M55 1A8.
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.affiliation: Institute for Clinical and Molecular Virology, Erlangen University Medical School, Schlossgarten 4, D-91054 Erlangen, Germany; Institute of Genetics, University of Cologne, D-50674 Cologne, Germany. Electronic address: walter.doerfler@viro.med.uni-erlangen.de.
authors.forename: Walter
authors.initials: W
authors.lastname: Doerfler
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D016679:Genome, Viral; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D011533:Proviruses / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
chemical_list: D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide
keywords: Bisulfite sequencing; Epigenetics of HIV-1 proviral DNA; Escape from proviral DNA methylation; Fluctuation of CpG methylation in one LTNP individual; Integrated HIV-1 DNA in PBMC's from infected individuals; Methylation analysis of integrated HIV-1 genomes; Predominance of unmethylated CpG's in PBMC's; Wide spectrum of infection outcome