title: APOBEC3B deletion and risk of HIV-1 acquisition.
abstract: The human APOBEC3 family of cytidine deaminases provides intrinsic immunity to retroviral infection. A naturally occurring 29.5-kb deletion removes the entire APOBEC3B gene. We examined the impact of the APOBEC3B gene deletion in >4000 individuals from 5 human immunodeficiency virus type 1 (HIV-1) natural history cohorts. The hemizygous genotype had no effect on either acquisition of HIV-1 infection or progression to AIDS. However, the homozygous deletion was significantly associated with unfavorable outcomes for HIV-1 acquisition (odds ratio, 7.37; P= .024), progression to AIDS (relative hazard, 4.01; P=. 03), and viral set point (P= .04). These findings suggest that the loss of APOBEC3B may increase host susceptibility to HIV-1 acquisition and progression to AIDS and warrant further study.
authors.affiliation: Laboratory of Genomic Diversity, SAIC-Frederick, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: Randall
authors.initials: R
authors.lastname: Johnson
authors.forename: John
authors.initials: J
authors.lastname: Phair
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
authors.forename: Sharyne
authors.initials: S
authors.lastname: Donfield
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
mesh_terms: D003564:Cytidine Deaminase / Q000235:genetics*; D005006:Ethnicity; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015778:Minor Histocompatibility Antigens
chemical_list: D015778:Minor Histocompatibility Antigens; C495794:APOBEC3B protein, human; D003564:Cytidine Deaminase
references.citation: Nat Genet. 2004 Jun;36(6):565-74
references.pmid: 15167933
references.citation: Virology. 2005 Sep 1;339(2):281-8
references.pmid: 15993456
references.citation: AIDS Res Hum Retroviruses. 2005 Jul;21(7):611-9
references.pmid: 16060832
references.citation: PLoS Genet. 2007 Apr 20;3(4):e63
references.pmid: 17447845
references.citation: JAMA. 2006 Sep 27;296(12):1498-506
references.pmid: 17003398
references.citation: Curr Biol. 2004 Aug 10;14(15):1392-6
references.pmid: 15296758
references.citation: J Virol. 2004 Oct;78(20):11070-6
references.pmid: 15452227
references.citation: Stat Med. 1995 Oct 15;14(19):2143-60
references.pmid: 8552893
references.citation: Nat Genet. 2006 Aug;38(8):904-9
references.pmid: 16862161
references.citation: J Virol. 2004 Jun;78(11):6073-6
references.pmid: 15141007
references.citation: PLoS Genet. 2007 Jan 26;3(1):e19
references.pmid: 17257057
references.citation: J Biol Chem. 2004 Dec 17;279(51):53379-86
references.pmid: 15466872
references.citation: Nature. 2002 Aug 8;418(6898):646-50
references.pmid: 12167863
references.citation: Virology. 2007 Aug 1;364(2):486-93
references.pmid: 17434555
references.citation: J Virol. 2005 Aug;79(15):9579-87
references.pmid: 16014920