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性传播和非肠道病毒传播后HIV-1基因组RNA的多样化

HIV-1 genomic RNA diversification following sexual and parenteral virus transmission.

作者信息

Wolfs T F, Zwart G, Bakker M, Goudsmit J

机构信息

Human Retrovirus Laboratory, Academic Medical Centre, Amsterdam, The Netherlands.

出版信息

Virology. 1992 Jul;189(1):103-10. doi: 10.1016/0042-6822(92)90685-i.

DOI:10.1016/0042-6822(92)90685-i
PMID:1376536
Abstract

Human immunodeficiency virus type 1 (HIV-1) genomic RNA variation was studied in seven presumed donor-recipient pairs directly following sexual (6/7) or parenteral (1/7) transmission. The first RNA-positive serum sample of each recipient and the serum sample of the virus transmitter, identified by epidemiological history and taken within a time bracket of three months of the recipient seroconversion, were analyzed by polymerase chain reaction amplification followed by sequencing of eight cDNA clones of 276 bp, including the V3 coding region. The sequence populations of the recipients were without exception homogeneous, while the sequence populations of the transmitters showed varying degrees of heterogeneity. Nucleotide distance between consensus sequences of unrelated individuals from the Amsterdam population (interpatient variation) averaged 11% (range 7-15%). The largest distance between two clonal sequences of one individual (intrapatient variation) was also 11%. Consensus sequences of five recipients differed by only 0-1% from the consensus sequence of the presumed transmitter, including two pairs of which the transmission was either proven or highly probable. This contrasted with a difference of 10-12% in two pairs, casting doubt on the epidemiological relatedness. Antibody reactivity to a panel of V3 peptides with varying degrees of similarity to the V3 sequences obtained did not augment the discriminatory power of sequence analysis. Results of the sequential sequencing of samples of one transmitter suggest that this was due to an anamnestic antibody response of the transmitter to early variants. From the loss of sequence heterogeneity following transmission and the consensus sequence similarities observed within five transmitter-recipient pairs, we conclude that HIV-1 transmission results in the selection of a limited number of genomes carrying on the infection in the new host, but does not generally lead to a shift in the sequence population as defined by the consensus sequence.

摘要

在7对推测的供体 - 受体对中,对1型人类免疫缺陷病毒(HIV - 1)基因组RNA变异进行了研究,这些对是在性传播(6/7)或非肠道传播(1/7)后直接进行研究的。通过聚合酶链反应扩增,随后对276 bp的8个cDNA克隆(包括V3编码区)进行测序,分析了每个受体的首个RNA阳性血清样本以及通过流行病学史确定且在受体血清转化后三个月内采集的病毒传播者的血清样本。受体的序列群体无一例外都是同质的,而传播者的序列群体则表现出不同程度的异质性。来自阿姆斯特丹人群的不相关个体的共有序列之间的核苷酸距离(患者间变异)平均为11%(范围为7 - 15%)。一个个体的两个克隆序列之间的最大距离(患者内变异)也是11%。5名受体的共有序列与推测传播者的共有序列仅相差0 - 1%,其中包括两对传播已被证实或极有可能的情况。这与另外两对相差10 - 12%形成对比,使人对流行病学关联性产生怀疑。对一组与所获得的V3序列具有不同程度相似性的V3肽的抗体反应性并未增强序列分析的鉴别能力。对一名传播者样本的连续测序结果表明,这是由于传播者对早期变异产生的回忆性抗体反应所致。从传播后序列异质性的丧失以及在5对传播者 - 受体对中观察到的共有序列相似性,我们得出结论,HIV - 1传播导致在新宿主中选择有限数量的携带感染的基因组,但一般不会导致由共有序列定义的序列群体发生转变。

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