title: Effect of HIV-1 Vif variability on progression to pediatric AIDS and its association with APOBEC3G and CUL5 polymorphisms.
abstract: The APOBEC3G protein is a restriction factor that can inhibit the replication of HIV-1. The virus has the capacity to counteract this antiviral activity through the expression of the Vif accessory protein, which recruits a CUL5-based ubiquitin ligase complex that determines APOBEC3G proteasomal degradation. In this work we evaluated in a large pediatric cohort (i) whether single nucleotide polymorphisms of APOBEC3G and CUL5 genes (APOBEC3G H186R, APOBEC3G C40693T and CUL5 SNP6) can alter the risk of HIV-1 vertical transmission and/or the rate of progression to AIDS, (ii) the effect of HIV-1 Vif variants on the clinical course of disease, and (iii) whether the patient genotype for the studied polymorphisms could have an impact on Vif characteristics. We found no effect of the studied APOBEC3G or CUL5 genetic variants on vertical transmission or progression to pediatric AIDS. However, we detected an association of certain Vif alterations (a one amino acid insertion at position 61 and the substitutions A62D/N/S and Q136P) with an accelerated AIDS outcome. Additionally, we observed that the APOBEC3G C40693T and CUL5 SNP6 minor alleles were correlated with substitutions in Vif motifs that are involved in the interaction with APOBEC3G and CUL5 proteins, respectively. Our results suggest that Vif alterations may contribute to a rapid AIDS onset and that Vif variability could be influenced by APOBEC3G and CUL5 polymorphisms in children.
authors.affiliation: Laboratorio de Biología Celular y Retrovirus - CONICET, Hospital de Pediatría Juan P. Garrahan, Ciudad de Buenos Aires, Argentina.
authors.forename: Federico A
authors.initials: FA
authors.lastname: De Maio
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Rocco
authors.forename: Paula C
authors.initials: PC
authors.lastname: Aulicino
authors.forename: Rosa
authors.initials: R
authors.lastname: Bologna
authors.forename: Andrea
authors.initials: A
authors.lastname: Mangano
authors.forename: Luisa
authors.initials: L
authors.lastname: Sen
mesh_terms: D000071480:APOBEC-3G Deaminase; D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000635:transmission; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D044842:Cullin Proteins / Q000235:genetics*; D003564:Cytidine Deaminase / Q000235:genetics*; D018450:Disease Progression; D056726:Genetic Association Studies; D014644:Genetic Variation; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D053208:Kaplan-Meier Estimate; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D055815:Young Adult; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: C496871:CUL5 protein, human; D044842:Cullin Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase