title: Elevated hypermutation levels in HIV-1 natural viral suppressors.
abstract: Mutations in the HIV-1 proviral genomes delay the progression of the disease. We compared the mutation status in full-length proviral genomes of 23 HIV-infected patients with undetectable viral loads in the absence of therapy named natural viral suppressors (NVS) or Elite Controllers with 23 HIV-infected controls (10 patients on HAART treatment and 13 untreated patients). Provirus DNA was extracted from PBMC for amplification and sequencing to determine the mutation status. Nine (39 %) of the 23 NVS patients had defective proviral genomes, compared to 4 of the treated controls (40%, p = 0.96) and only one of the untreated controls (8%, p = 0.059). Most of the defective genomes resulted from Gto-A hypermutation. Among patients with hypermutation, the rate ratio for mutation was significantly higher for the NVS compared to treated controls (p = 0.043). Our data suggests that inactivation of the virus through the APOBEC3G system may contribute to the NVS phenotype.
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, United States 725 West Lombard Street Baltimore, MD 21201, USA. leyzaguirre@ihv.umaryland.edu
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Eyzaguirre
authors.forename: Manhattan
authors.initials: M
authors.lastname: Charurat
authors.forename: Robert R
authors.initials: RR
authors.lastname: Redfield
authors.forename: William A
authors.initials: WA
authors.lastname: Blattner
authors.forename: Jean K
authors.initials: JK
authors.lastname: Carr
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Sajadi
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D016679:Genome, Viral / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011533:Proviruses / Q000235:genetics; D017422:Sequence Analysis, DNA; D038301:Virus Inactivation
chemical_list: D004279:DNA, Viral
keywords: Elite controllers; HIV-1; Hypermutation; Natural viral suppressors (NVS)