Compartmentalization of HIV-1 within the female genital tract is due to monotypic and low-diversity variants not distinct viral populations.
Compartmentalization of HIV-1 within the female genital tract is due to monotypic and low-diversity variants not distinct viral populations.
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雌性生殖道内HIV-1的隔室化是由于单型和低多样性变体而不是不同的病毒群体引起的。
DOI：
10.1371/journal.pone.0007122
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发表时间：
2009-09-22
期刊：
影响因子：
3.7
通讯作者：
Frenkel L
中科院分区：
文献类型：
--
作者：
Bull M;Learn G;Genowati I;McKernan J;Hitti J;Lockhart D;Tapia K;Holte S;Dragavon J;Coombs R;Mullins J;Frenkel L
在12项主要使用无细胞病毒的研究中，57名妇女中有一半人注意到生殖道和血液之间的HIV-1区室化。为了进一步了解慢性HIV-1感染妇女的生殖道和血液病毒之间的差异，对这些组织中的无细胞和细胞相关病毒群体进行测序，推断整合的病毒DNA包括感染早期存档的变体，并提供了更多的基因型进行比较。在一项横断面研究中，对来自每个妇女生殖道和血液的HIV-1 RNA和DNA的单基因组扩增的多个序列进行了比较。使用四种统计检验评价了最大似然概率的划分证据。通过≥2次统计分析，7/13例女性的生殖道和血液HIV-1出现区室化。这些受试者的基因组图的特征是低多样性生殖器特异性病毒进化枝散布在含有生殖器和血液序列的进化枝之间。许多生殖器特异性分支含有单型HIV-1序列。在2/7的妇女中，HIV-1人群在所有四个统计测试中被显著划分;两者都具有低多样性的生殖道分支。将单型变体折叠成单个序列减少了区室化的普遍性和程度。病毒序列没有表现出组织特异性签名氨基酸残基，差异免疫选择，或共受体的使用。在慢性HIV-1感染的女性中，多个相同的序列表明HIV-1感染细胞的增殖，并且低多样性的组织特异性系统发育分支与病毒复制的爆发一致。这些单型和组织特异性病毒为HIV-1在女性生殖道和血液之间的区室化提供了统计学支持。然而，这些分支与由生殖器和血液序列组成的分支的混合以及组织特异性遗传特征的缺乏表明血液和生殖道之间的区室化可能是由于病毒复制和感染细胞的增殖，并质疑女性生殖道中的HIV-1是否与血液不同。
Compartmentalization of HIV-1 between the genital tract and blood was noted in half of 57 women included in 12 studies primarily using cell-free virus. To further understand differences between genital tract and blood viruses of women with chronic HIV-1 infection cell-free and cell-associated virus populations were sequenced from these tissues, reasoning that integrated viral DNA includes variants archived from earlier in infection, and provides a greater array of genotypes for comparisons. Multiple sequences from single-genome-amplification of HIV-1 RNA and DNA from the genital tract and blood of each woman were compared in a cross-sectional study. Maximum likelihood phylogenies were evaluated for evidence of compartmentalization using four statistical tests. Genital tract and blood HIV-1 appears compartmentalized in 7/13 women by ≥2 statistical analyses. These subjects' phylograms were characterized by low diversity genital-specific viral clades interspersed between clades containing both genital and blood sequences. Many of the genital-specific clades contained monotypic HIV-1 sequences. In 2/7 women, HIV-1 populations were significantly compartmentalized across all four statistical tests; both had low diversity genital tract-only clades. Collapsing monotypic variants into a single sequence diminished the prevalence and extent of compartmentalization. Viral sequences did not demonstrate tissue-specific signature amino acid residues, differential immune selection, or co-receptor usage. In women with chronic HIV-1 infection multiple identical sequences suggest proliferation of HIV-1-infected cells, and low diversity tissue-specific phylogenetic clades are consistent with bursts of viral replication. These monotypic and tissue-specific viruses provide statistical support for compartmentalization of HIV-1 between the female genital tract and blood. However, the intermingling of these clades with clades comprised of both genital and blood sequences and the absence of tissue-specific genetic features suggests compartmentalization between blood and genital tract may be due to viral replication and proliferation of infected cells, and questions whether HIV-1 in the female genital tract is distinct from blood.
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6.4
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