title: Expression of APOBEC3G/3F and G-to-A hypermutation levels in HIV-1-infected children with different profiles of disease progression.
abstract: OBJECTIVE
  Increasing evidence has accumulated showing the role of APOBEC3G (A3G) and 3F (A3F) in the control of HIV-1 replication and disease progression in humans. However, very few studies have been conducted in HIV-infected children. Here, we analyzed the levels of A3G and A3F expression and induced G-to-A hypermutation in a group of children with distinct profiles of disease progression.
  
  
  RESULTS
  Perinatally HIV-infected children were classified as progressors or long-term non-progressors according to criteria based on HIV viral load and CD4 T-cell counts over time. A group of uninfected control children were also enrolled in the study. PBMC proviral DNA was assessed for G-to-A hypermutation, whereas A3G and A3F mRNA were isolated and quantified through TaqMan® real-time PCR. No correlation was observed between disease progression and A3G/A3F expression or hypermutation levels. Although all children analyzed showed higher expression levels of A3G compared to A3F (an average fold of 5 times), a surprisingly high A3F-related hypermutation rate was evidenced in the cohort, irrespective of the child's disease progression profile.
  
  
  CONCLUSIONS
  Our results contribute to the current controversy as to whether HIV disease progression is related to A3G/A3F enzymatic activity. To our knowledge, this is the first study analyzing A3G/F expression in HIV-infected children, and it may pave the way to a better understanding of the host factors governing HIV disease in the pediatric setting.
authors: Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Nívea D
authors: ND
authors: Amoêdo
authors: Adriana O
authors: AO
authors: Afonso
authors: Sílvia M
authors: SM
authors: Cunha
authors: Ricardo H
authors: RH
authors: Oliveira
authors: Elizabeth S
authors: ES
authors: Machado
authors: Marcelo A
authors: MA
authors: Soares
mesh_terms: D000071480:APOBEC-3G Deaminase; D002648:Child; D002675:Child, Preschool; D003564:Cytidine Deaminase / Q000235:genetics*; D043525:Cytosine Deaminase / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D018450:Disease Progression; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D007223:Infant; D009154:Mutation; D011533:Proviruses / Q000235:genetics / Q000472:pathogenicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D012333:RNA, Messenger; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase