HIV Type 1 Mother-to-Child Transmission Facilitated by Distinctive Glycosylation Sites in the gp120 Envelope Glycoprotein

HIV Type 1 Mother-to-Child Transmission Facilitated by Distinctive Glycosylation Sites in the gp120 Envelope Glycoprotein
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DOI:
10.1089/aid.2011.0023
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发表时间:
2012-07-01
影响因子:
1.5
通讯作者:
Paxton, William A.
Paxton, William A.
中科院分区:
医学4区
文献类型:
--
作者:
Baan, Elly;de Ronde, Anthony;Paxton, William A.

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人类免疫缺陷病毒1型(HIV-1)与母婴传播(MTCT)相关的特征仍然知之甚少。我们研究了一组来自卢旺达的30名感染HIV-1亚型A或C病毒的母亲,其中7人在怀孕期间或出生后不久感染了他们的孩子。CD 4计数和病毒载量在非传播母亲(NTM)与传播母亲(TM)组之间没有显著差异。与早期研究相反,我们不仅分析和比较了TM及其感染儿童中发现的病毒gp 120包膜V1-V5区域的基因型特征,而且还包括来自NTM的数据。在V1-V2和V1-V5区的潜在N-糖基化位点(PNGS)的长度和数量方面没有发现差异。我们鉴定出在AA 234和AA 339位置上具有PNGS的病毒优选传播,而具有PNGS-N295的病毒在传播中显示出劣势。我们还发现,在TM和感染儿童的病毒中,PNGS-N339的频率显著高于我们队列中的NTM和通过性传播的病毒的频率,而在儿童中,PNGS-N295的频率显著低于TM和急性水平感染的频率。总的来说,我们的研究结果提供了证据表明,在考虑MTCT时,在gp 120包膜中PNGS-N339位点的存在和PNGS-N295位点的缺失赋予HIV-1优势。
The human immunodeficiency virus type 1 (HIV-1) characteristics associated with mother-to-child transmission (MTCT) are still poorly understood. We studied a cohort of 30 mothers from Rwanda infected with HIV-1 subtype A or C viruses of whom seven infected their children either during gestation or soon after birth. CD4 counts and viral load did not significantly differ between nontransmitting mother (NTM) versus transmitting mother (TM) groups. In contrast to earlier studies we not only analyzed and compared the genotypic characteristics of the V1-V5 region of the gp120 envelope of viruses found in TM and their infected children, but also included data from the NTM. No differences were found with respect to length and number of potential N-glycosylation sites (PNGS) in the V1-V2 and the V1-V5 region. We identified that viruses with a PNGS on positions AA234 and AA339 were preferably transmitted and that viruses with PNGS-N295 showed a disadvantage in transmission. We also showed that the frequency of PNGS-N339 in the viruses of TM and infected children was significantly higher than the frequency in NTM in our cohort and in viruses undergoing sexual transmission while the frequency of PNGS-N295 in children was significantly lower than the frequency in TM and acute horizontal infections. Collectively, our results provide evidence that the presence of the PNGS-N339 site and absence of the PNGS-N295 site in the gp120 envelope confers an advantage to HIV-1 when considering MTCT.