Neilson J R, John G C, Carr J K, Lewis P, Kreiss J K, Jackson S, Nduati R W, Mbori-Ngacha D, Panteleeff D D, Bodrug S, Giachetti C, Bott M A, Richardson B A, Bwayo J, Ndinya-Achola J, Overbaugh J
Departments of Microbiology, University of Washington, Seattle, Washington, USA.
J Virol. 1999 May;73(5):4393-403. doi: 10.1128/JVI.73.5.4393-4403.1999.
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.
在撒哈拉以南非洲地区，1型人类免疫缺陷病毒（HIV-1）造成的影响最为严重，该病毒存在多种亚型。非洲人群中不同亚型的分布通常与特定的风险行为无关。因此，非洲是一个理想的研究环境，可在人群层面上研究来自不同亚型的病毒的多样性和混合情况。在这种环境下，还可以探讨感染特定亚型是否与疾病阶段的差异有关。为了解决这些问题，我们分析了来自肯尼亚内罗毕的320名女性的HIV-1亚型、血浆病毒载量和CD4淋巴细胞水平。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法确定亚型，使用来自不同地理区域的亚型参考序列以及肯尼亚已知亚型的包膜序列。该人群中各亚型的分布如下：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%）。在所分析的序列中，2.2%检测到了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以及非洲其他存在多种亚型的地区可能非常普遍。感染C亚型病毒的女性血浆病毒RNA水平最高，且感染C亚型病毒的女性CD4淋巴细胞水平显著低于感染其他亚型的女性。这些数据共同表明，肯尼亚感染C亚型病毒的女性比感染A或D亚型的女性处于更严重的免疫抑制阶段。至少有两种模型可以解释这项横断面研究的数据；一种是感染C亚型与疾病进展更快有关，另一种是C亚型代表了肯尼亚更古老的疫情。在纵向研究中区分这些可能性对于增进我们对特定亚型在HIV-1传播和发病机制中的作用的理解至关重要。
