Evaluation of cervical mucosa in transmission bottleneck during acute HIV-1 infection using a cervical tissue-based organ culture.

Evaluation of cervical mucosa in transmission bottleneck during acute HIV-1 infection using a cervical tissue-based organ culture.
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DOI:
10.1371/journal.pone.0032539
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Gupta P
Gupta P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shen C;Ding M;Ratner D;Montelaro RC;Chen Y;Gupta P

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虽然在慢性感染者中存在不同的HIV-1毒株,但只有一种或有限的病毒毒株成功地传播给新的个体。这种“传输瓶颈”的原因尚不清楚。使用人宫颈外植体模型来测量来自慢性感染的病毒株和传播者/创始者变体的HIV-1传播效率。我们还评估了接种物中HIV-1变异体的遗传特征,并与通过宫颈粘膜传播的HIV-1变异体进行了比较。本研究中使用了8种不同的HIV-1分离株,6种慢性分离株和2种传播者/创始者病毒。评估慢性和传播者/创始者病毒分离株的传播效率以及病毒传播前后慢性分离株的病毒多样性。结果表明,传播者/创始者病毒没有显示出比慢性HIV-1分离株更高的传播效率。此外,没有证据表明接种物和传播的病毒株之间存在多样性差异。系统发育分析表明,在接种物中的变异体的序列和那些存在于传播的病毒混合在一起,而不管共受体的使用。此外,接种物和传播的变体具有相似的成对距离分布。在器官培养模型中,HIV-1通过宫颈粘膜传播期间没有选择单一或有限数量的病毒变体,表明单独的宫颈粘膜可能不会产生体内观察到的HIV-1感染的传播瓶颈。
Although there are different strains of HIV-1 in a chronically infected individual, only one or limited virus strains are successfully transmitted to a new individual. The reason for this “transmission bottleneck” is as yet unknown. A human cervical explant model was used to measure HIV-1 transmission efficiency of viral strains from chronic infections, and transmitter/founder variants. We also evaluated the genetic characteristics of HIV-1 variants in the inoculums compared to those transmitted across the cervical mucosa. Eight different HIV-1 isolates were used in this study, six chronic isolates and two transmitter/founder viruses. The transmission efficiency of the chronic and transmitter/founder virus isolates and the viral diversity of chronic isolates before and after viral transmission were assessed. The results indicate that transmitter/founder viruses did not display higher transmission efficiency than chronic HIV-1 isolates. Furthermore, no evidence for a difference in diversity was found between the inoculums and transmitted virus strains. Phylogenetic analysis indicated that the sequences of variants in the inoculums and those present in transmitted virus intermingled irrespective of co-receptor usage. In addition, the inoculum and transmitted variants had a similar pairwise distance distribution. There was no selection of a single or limited number of viral variants during HIV-1 transmission across the cervical mucosa in the organ culture model, indicating that the cervical mucosa alone may not produce the transmission bottleneck of HIV-1 infection observed in vivo.
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