HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.
HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.
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DOI：
10.1371/journal.ppat.1000876
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发表时间：
2010-05-06
期刊：
影响因子：
6.7
通讯作者：
Fraser C
中科院分区：
文献类型：
--
作者：
Hollingsworth TD;Laeyendecker O;Shirreff G;Donnelly CA;Serwadda D;Wawer MJ;Kiwanuka N;Nalugoda F;Collinson-Streng A;Ssempijja V;Hanage WP;Quinn TC;Gray RH;Fraser C
据推测，HIV-1 病毒载量设定点是 HIV-1 病毒毒力的替代指标，并且它可能受到人类宿主群体的自然选择的影响。这一假设的一个关键检验是病毒载量设定点在传播个体和感染个体之间是否相关。我们回顾性地确定了乌干达拉凯队列中的 112 对 HIV 不一致的异性恋夫妇，其中怀疑存在 HIV 传播，并确定了病毒载量设定点。此外，序列数据可用于确定其中 57 对夫妇的遗传连锁传播。性别、年龄、病毒亚型、索引伴侣和自我报告的生殖器溃疡病状态（GUD）都是已知的。使用方差分析，我们估计了病毒载量设定点的方差比例，这可以通过夫妻内的相似性（“夫妻效应”）来解释。疑似夫妻内传播的个体（97对夫妇）具有相似的病毒载量设定点（p = 0.054单因素模型，p = 0.0057调整），夫妻效应解释了病毒载量的16％方差（调整后23％）。对 29 对具有强大遗传支持的夫妇进行了重复分析。夫妻效应是病毒载量设定点的主要决定因素（单因素 p = 0.067，调整后 p = 0.036），效应大小为 27%（调整后 37%）。具有流行病学关联且具有传播遗传支持的夫妇中的个体具有相似的病毒载量设定点。最简单的解释是，这是由于所传播的病毒具有共同的特征，这一发现揭示了病毒因素在 HIV-1 发病机制中的作用以及病毒的进化。在长期无症状感染 HIV-1 期间，感染者之间的病毒载量设定值存在相当大的差异。较高的病毒载量设定点会增加传染性并降低生存率。先前的研究表明，最常见的病毒载量设定点是那些中间病毒载量设定点，这些设定点会导致感染者一生中传播 HIV-1 的机会最多，从而平衡生存和传染性。最常见的病毒载量设定值与终生传播的最佳值之间的这种一致性可能是针对 HIV-1 的人群水平选择的结果。然而，只有当病毒载量设定点是病毒的遗传特征时，即传播夫妇双方的病毒载量设定点相似时，这种情况才会发生。通过研究异性夫妇之间的病毒载量设定点，我们发现这些夫妇的病毒载量设定点相似。当我们只研究那些具有强大的传播遗传支持的夫妇时，他们的病毒载量甚至比我们研究整个群体时更加相似。这些结果表明，存在从一个感染个体传递到下一个感染个体的病毒因子，这些病毒因子在确定病毒载量设定点方面发挥作用，并且群体水平的选择可以对这些病毒因子起作用。
It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD) were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the ‘couple effect’). Individuals with suspected intra-couple transmission (97 couples) had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted) and the couple effect explained 16% of variance in viral loads (23% adjusted). The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted) and the size of the effect was 27% (37% adjusted). Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus. During the long period of asymptomatic infection with HIV-1 there is considerable variability in viral load set-point between infected individuals. Higher viral load set-points increase infectivity and decrease survival. Previous work has shown that the most commonly observed viral load set-points are those intermediate viral load set-points which lead to the largest number of opportunities to transmit HIV-1 in an infectious person's lifetime, balancing survival and infectiousness. This coincidence between the most common viral load set-points and the optimum for lifetime transmission could be the result of population-level selection acting on HIV-1. However, this could only have happened if viral load set-point is a heritable characteristic of the virus, i.e. if viral load set-points are similar between both partners of transmitting couples. By studying viral load set-points amongst heterosexual couples, we show that viral load set-points are similar in these couples. When we study only those couples with strong genetic support for transmission, their viral loads are even more similar than when we study the whole group. These results suggest that there are viral factors which are passed from one infected individual to the next which play a role in determining viral load set-point and that population-level selection could act upon these viral factors.
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DOI：
10.1073/pnas.0708559104
发表时间：
2007-10-30
影响因子：
11.1
作者：
Fraser, Christophe;Hollingsworth, T. Deirdre;Hanage, William P.
通讯作者：
Hanage, William P.
影响因子：
--
作者：
Kivelä, PS;Krol, A;Ristola, MA
通讯作者：
Ristola, MA
影响因子：
5.4
作者：
Ariën, KK;Abraha, A;Arts, EJ
通讯作者：
Arts, EJ
DOI：
10.1084/jem.20082831
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Keele BF;Li H;Learn GH;Hraber P;Giorgi EE;Grayson T;Sun C;Chen Y;Yeh WW;Letvin NL;Mascola JR;Nabel GJ;Haynes BF;Bhattacharya T;Perelson AS;Korber BT;Hahn BH;Shaw GM
通讯作者：
Shaw GM
DOI：
10.1073/pnas.0802203105
发表时间：
2008-05-27
影响因子：
11.1
作者：
Keele, Brandon F.;Giorgi, Elena E.;Shaw, George M.
通讯作者：
Shaw, George M.