Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
PLoS One. 2011;6(8):e24118. doi: 10.1371/journal.pone.0024118. Epub 2011 Aug 29.
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.
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.
越来越多的证据表明 APOBEC3G（A3G）和 3F（A3F）在控制 HIV-1 复制和人类疾病进展方面发挥作用。然而，在 HIV 感染儿童中进行的研究很少。在这里，我们分析了一组具有不同疾病进展特征的儿童中 A3G 和 A3F 表达水平以及诱导的 G-to-A 超突变。
方法/主要发现：根据基于 HIV 病毒载量和 CD4 T 细胞计数随时间变化的标准，将围产期感染 HIV 的儿童分类为进展者或长期非进展者。还招募了一组未感染的对照儿童。评估 PBMC 前病毒 DNA 的 G-to-A 超突变，同时通过 TaqMan®实时 PCR 分离和定量 A3G 和 A3F mRNA。疾病进展与 A3G/A3F 表达或超突变水平之间没有相关性。尽管所有分析的儿童与 A3F 相比，A3G 的表达水平更高（平均倍数为 5 倍），但在该队列中，无论儿童的疾病进展情况如何，都发现了惊人的高 A3F 相关超突变率。
我们的研究结果对 HIV 疾病进展是否与 A3G/A3F 酶活性有关的当前争议做出了贡献。据我们所知，这是第一项分析 HIV 感染儿童中 A3G/F 表达的研究，它可能为更好地理解宿主因素在儿科环境中控制 HIV 疾病铺平道路。
