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. 2011;6(8):e24118.
doi: 10.1371/journal.pone.0024118. Epub 2011 Aug 29.

Expression of APOBEC3G/3F and G-to-A hypermutation levels in HIV-1-infected children with different profiles of disease progression

Nívea D Amoêdo  1 , Adriana O Afonso, Sílvia M Cunha, Ricardo H Oliveira, Elizabeth S Machado, Marcelo A Soares
Affiliations

Expression of APOBEC3G/3F and G-to-A hypermutation levels in HIV-1-infected children with different profiles of disease progression

Nívea D Amoêdo et al. PLoS One. 2011.

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.

Methodology/principal findings: 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.

Conclusion: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. APOBEC3G (A) and APOBEC3F (B) mRNA expression levels relative to GAPDH mRNA copy numbers of patients with or without evidenced hypermutation.
Horizontal bars depict the median value for each group.
Figure 2
Figure 2. APOBEC3G (A) and APOBEC3G (B) mRNA expression levels relative to GAPDH mRNA copy numbers of patients with different profiles of HIV disease progression.
Horizontal bars depict the median value for each group.
Figure 3
Figure 3. Average APOBEC3G to APOBEC3F mRNA expression levels quantified from eight HIV+ children (6 progressors and 2 nonprogressors) and five HIV− controls.
A3F expression levels were arbitrarily set at 1.
Figure 4
Figure 4. APOBEC3G and APOBEC3F mRNA expression levels relative to GAPDH mRNA copy numbers comparing patients stratified according to antiretroviral treatment exposure (A) and HIV viral load (B).
Horizontal bars depict the median value for each group.
See this image and copyright information in PMC

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