Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya
Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya
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DOI：
10.1128/jvi.73.5.4393-4403.1999
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发表时间：
1999-05-01
影响因子：
5.4
通讯作者：
Overbaugh, J
中科院分区：
文献类型：
--
作者：
Neilson, JR;John, GC;Overbaugh, J
在撒哈拉以南非洲，人类免疫缺陷病毒1型(HIV-1)的影响最具破坏性，该病毒有多个亚型。非洲人群中不同亚型的分布通常与特定的危险行为无关。因此，非洲是在人口基础上检查不同亚型病毒的多样性和混合情况的理想环境。在这种情况下，也可以解决感染特定亚型是否与疾病阶段的差异有关的问题。为了解决这些问题，我们分析了来自肯尼亚内罗毕的320名妇女的HIV-1亚型、血浆病毒载量和CD4淋巴细胞水平。亚型是通过异源双链迁移率分析和包膜基因序列分析相结合的方式确定的，使用地理上不同的亚型参考序列以及来自肯尼亚的已知亚型的包膜序列。亚型分布：A亚型225例(70.3%)，D亚型65例(20.5%)，C亚型22例(6.9%)，G亚型1例(0.3%)。在分析的序列中，有2.2%的序列检测到亚型间重组包膜基因。鉴于所分析的序列仅代表前病毒基因组的一小部分，这表明亚型间重组病毒基因组在肯尼亚和非洲其他有多个亚型的地区可能非常常见。感染C亚型病毒的妇女血浆病毒RNA水平最高，而感染C亚型病毒的妇女的CD4淋巴细胞水平显著低于其他亚型感染的妇女。总而言之，这些数据表明，在肯尼亚，感染C亚型病毒的女性比感染A或D亚型病毒的女性处于更严重的免疫抑制阶段。至少有两个模型可以解释这项横断面研究的数据；一个是感染C亚型病毒与更快的疾病进展相关，第二是C亚型病毒代表着肯尼亚的一种较老的流行病。在纵向研究中区分这些可能性对于增加我们对特定亚型在HIV-1传播和发病机制中的作用的了解将是重要的。
In sub-Saharan Africa, where the effects of human immunodeficiency virus type 1 (HIV-1) have been most devastating, there are multiple subtypes of this virus. The distribution of different subtypes within African populations is generally not linked to particular risk behaviors. Thus, Africa is an ideal setting in which to examine the diversity and mixing of viruses from different subtypes on a population basis. In this setting, it is also possible to address whether infection with a particular subtype is associated with differences in disease stage. To address these questions, we analyzed the HIV-1 subtype, plasma viral loads, and CD4 lymphocyte levels in 320 women from Nairobi, Kenya. Subtype was determined by a combination of heteroduplex mobility assays and sequence analyses of envelope genes, using geographically diverse subtype reference sequences as well as envelope sequences of known subtype from Kenya. The distribution of subtypes in this population was as follows: subtype A, 225 (70.3%); subtype D, 65 (20.5%); subtype C, 22 (6.9%); and subtype G, 1 (0.3%). Intersubtype recombinant envelope genes were detected in 2.2% of the sequences analyzed. Given that the sequences analyzed represented only a small fraction of the proviral genome, this suggests that intersubtype recombinant viral genomes may be very common in Kenya and in other parts of Africa where there are multiple subtypes. The plasma viral RNA levels were highest in women infected with subtype C virus, and women infected with subtype C virus had significantly lower CD4 lymphocyte levels than women infected with the other subtypes. Together, these data suggest that women in Kenya who are infected with subtype C viruses are at more advanced stages of immunosuppression than women infected with subtype A or D. There are at least two models to explain the data from this cross-sectional study; one is that infection with subtype C is associated with a more rapid disease progression, and the second is that subtype C represents an older epidemic in Kenya. Discriminating between these possibilities in a longitudinal study will be important for increasing our understanding of the role of specific subtypes in the transmission and pathogenesis of HIV-1.