APOBEC3G levels predict rates of progression to AIDS.
APOBEC3G levels predict rates of progression to AIDS.
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DOI：
10.1186/1742-4690-4-20
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发表时间：
2007-03-20
期刊：
影响因子：
3.3
通讯作者：
Smith H
中科院分区：
文献类型：
--
作者：
Jin X;Wu H;Smith H
APOBEC 3G（hA 3G）是一种新发现的天然免疫细胞因子，在体外抑制HIV复制。hA 3G是否在体内赋予抗HIV的保护作用尚不清楚。为了研究hA 3G在体内可能的抗HIV活性，我们检测了从HIV感染或HIV未感染个体分离的原代人细胞中的hA 3G mRNA丰度，发现hA 3G mRNA水平遵循长期非进展者> HIV未感染者>进展者的层次顺序;并且，hA 3G mRNA丰度与HIV疾病进展的替代物：病毒载量和CD 4计数相关。另一组后来证实，HIV感染者的hA 3G mRNA水平低于HIV未感染者，但没有发现hA 3G mRNA水平与病毒载量或CD 4计数之间的相关性。这些相互矛盾的结果表明，迫切需要对不同患者队列中的hA 3G表达水平进行更全面、结论性的研究。为了探索hA 3G丰度是否可能影响HIV疾病的进展，我们提出了一个假设，包括两个部分：a）在体内，每个PBMC的基础hA 3G mRNA表达水平是恒定的-具有微小的生理波动-由健康个体中的宿主遗传和表观遗传因素决定;并且群体中的基础hA 3G mRNA表达水平遵循正常水平。（或高斯）分布; B）尽管HIV随机感染，但其导致具有较低hA 3 G mRNA水平的那些人的疾病进展更快，而具有较高hA 3 G mRNA水平的那些人的疾病进展更慢。这一假设可以通过一组直接的实验来检验，这些实验比较了未感染HIV的健康个体和感染HIV的、未接受过抗逆转录病毒治疗的受试者（感染的早期和晚期）中hA 3G mRNA水平的分布。验证这一假设将对生物医学研究产生重大影响。a）它将hA 3G与长期非进展者中疾病进展较慢的潜在机制联系起来。B）hA 3G丰度测定可能有助于建立一种新的HIV感染者预后指标。
APOBEC3G (hA3G) is a newly discovered cellular factor of innate immunity that inhibits HIV replication in vitro. Whether hA3G conferrs protection against HIV in vivo is not known. To investigate the possible anti-HIV activity of hA3G in vivo, we examined hA3G mRNA abundance in primary human cells isolated from either HIV-infected or HIV-uninfected individuals, and found that hA3G mRNA levels follow a hierarchical order of long-term nonprogressors>HIV-uninfected>Progressors; and, hA3G mRNA abundance is correlated with surrogates of HIV disease progression: viral load and CD4 count. Another group later confirmed that HIV-infected subjects have lower hA3G mRNA levels than HIV-uninfected controls, but did not find correlations between hA3G mRNA levels and viral load or CD4 count. These conflicing results indicate that a more comprehensive, conclusive investigation of hA3G expression levels in various patient cohorts is urgently needed. For exploring whether hA3G abundance might influence HIV disease progression, we have formulated a hypothesis that inlcudes two parts: a) in vivo, the basal hA3G mRNA expression level per PBMC is a constant – with minor physiologic fluctuations – determined by host genetic and epigenetic elements in a healthy individual; and that the basal hA3G mRNA expression levels in a population follow a Normal (or Gaussian) distribution; b) that although HIV infects randomly, it results in more rapid disease progression in those with lower hA3G mRNA levels, and slower disease progression in those with higher hA3G mRNA levels. This hypothesis could be tested by a straighforward set of experiments to compare the distribution of hA3G mRNA levels in HIV-uninfected healthy individuals and that in HIV-infected, antiretroviral therapy-naïve subjects who are at early and late stages of infection. Testing this hypothesis will have significant implications for biomedical research. a) It will link hA3G to the mechanisms underlying slower disease progression in long-term nonprogressors. And, b) It may help to establiseh a new prognostic marker, the hA3G abundance measurement, for HIV-infected patients.
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