Lack of association between intact/deletion polymorphisms of the APOBEC3B gene and HIV-1 risk

PLoS One. 2014 Mar 25;9(3):e92861. doi: 10.1371/journal.pone.0092861. eCollection 2014.

Abstract

Objective: The human APOBEC3 family of proteins potently restricts HIV-1 replication APOBEC3B, one of the family genes, is frequently deleted in human populations. Two previous studies reached inconsistent conclusions regarding the effects of APOBEC3B loss on HIV-1 acquisition and pathogenesis. Therefore, it was necessary to verify the effects of APOBEC3B on HIV-1 infection in vivo.

Methods: Intact (I) and deletion (D) polymorphisms of APOBEC3B were analyzed using PCR. The syphilis, HBV and HCV infection rates, as well as CD4(+) T cell counts and viral loads were compared among three APOBEC3B genotype groups (I/I, D/I, and D/D). HIV-1 replication kinetics was assayed in vitro using primary cells derived from PBMCs.

Results: A total of 248 HIV-1-infected Japanese men who have sex with men (MSM) patients and 207 uninfected Japanese MSM were enrolled in this study. The genotype analysis revealed no significant differences between the APOBEC3B genotype ratios of the infected and the uninfected cohorts (p = 0.66). In addition, HIV-1 disease progression parameters were not associated with the APOBEC3B genotype. Furthermore, the PBMCs from D/D and I/I subjects exhibited comparable HIV-1 susceptibility.

Conclusion: Our analysis of a population-based matched cohort suggests that the antiviral mechanism of APOBEC3B plays only a negligible role in eliminating HIV-1 in vivo.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People
  • Cohort Studies
  • Cytidine Deaminase / genetics*
  • Genetic Predisposition to Disease*
  • HIV Infections / genetics*
  • HIV-1*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Polymorphism, Genetic*

Substances

  • Minor Histocompatibility Antigens
  • APOBEC3B protein, human
  • Cytidine Deaminase

Grants and funding

This work was partly supported by a grant from the National Hospital Organization Network (grant NHO H23-AIDS) and by grants for HIV/AIDS research from the Ministry of Health, Labor, and Welfare of Japan (grants H22-AIDS-004 and H24-AIDS-005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripts.