APOBEC3B deletion and risk of HIV-1 acquisition.

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.

[1]  B. Cullen,et al.  The intrinsic antiretroviral factor APOBEC3B contains two enzymatically active cytidine deaminase domains. , 2007, Virology.

[2]  E. Eichler,et al.  Population Stratification of a Common APOBEC Gene Deletion Polymorphism , 2007, PLoS genetics.

[3]  J. Goedert,et al.  Polymorphisms of CUL5 Are Associated with CD4+ T Cell Loss in HIV-1 Infected Individuals , 2007, PLoS genetics.

[4]  David R Bangsberg,et al.  Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. , 2006, JAMA.

[5]  D. Reich,et al.  Principal components analysis corrects for stratification in genome-wide association studies , 2006, Nature Genetics.

[6]  B. Cullen,et al.  Human APOBEC3B is a potent inhibitor of HIV-1 infectivity and is resistant to HIV-1 Vif. , 2005, Virology.

[7]  Xiao-Fang Yu,et al.  Regulation of Apobec3F and Human Immunodeficiency Virus Type 1 Vif by Vif-Cul5-ElonB/C E3 Ubiquitin Ligase , 2005, Journal of Virology.

[8]  M. Marin,et al.  Regulated production and anti-HIV type 1 activities of cytidine deaminases APOBEC3B, 3F, and 3G. , 2005, AIDS research and human retroviruses.

[9]  R. König,et al.  APOBEC3B and APOBEC3C Are Potent Inhibitors of Simian Immunodeficiency Virus Replication* , 2004, Journal of Biological Chemistry.

[10]  Amalio Telenti,et al.  APOBEC3G Genetic Variants and Their Influence on the Progression to AIDS , 2004, Journal of Virology.

[11]  M. Malim,et al.  Cytidine Deamination of Retroviral DNA by Diverse APOBEC Proteins , 2004, Current Biology.

[12]  Takeshi Kurosu,et al.  Human APOBEC3F Is Another Host Factor That Blocks Human Immunodeficiency Virus Type 1 Replication , 2004, Journal of Virology.

[13]  Stephen J O'Brien,et al.  Human genes that limit AIDS , 2004, Nature Genetics.

[14]  M. Malim,et al.  Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein , 2002, Nature.

[15]  Nitin R. Patel,et al.  Exact logistic regression: theory and examples. , 1995, Statistics in medicine.