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首页> 外文期刊>AIDS Research and Human Retroviruses >Longitudinal ultradeep characterization of HIV type 1 R5 and X4 subpopulations in patients followed from primary infection to coreceptor switch
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Longitudinal ultradeep characterization of HIV type 1 R5 and X4 subpopulations in patients followed from primary infection to coreceptor switch

机译：从原发感染到共受体转换，对患者的HIV 1 R5和X4亚型进行纵向超深表征

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摘要

In early infection HIV-1 generally uses the CCR5 coreceptor. During disease progression the coreceptor use switches to include CXCR4 in approximately 70% of infected individuals. The primary determinant for coreceptor use is located in the V3 loop of the viral envelope. Here, ultradeep pyrosequencing (UDPS) of the V3 loop was used to investigate if CXCR4-using (X4) virus may be present as a minority population during primary HIV infection (PHI). Three patients with HIV populations that switched coreceptor use, as determined by the MT-2 cell culture assay, were investigated. Longitudinally collected plasma samples (four to nine samples per patient) obtained from PHI until after coreceptor switch were analyzed by UDPS of the V3 loop. From each sample between 279 and 32,094 reads were generated based on template molecule availability. UDPS analysis showed that the X4 virus that emerged after switch was not present during PHI or prior to overt phenotypic switch. In addition, the phylogenetic analyses indicated that the X4 populations originated from R5 variants that had evolved after the previous R5-only sample was obtained. Finally, one to three major variants were found during PHI, supporting the idea that infection is established with one or just a few viral particles.
机译：在早期感染中，HIV-1通常使用CCR5共受体。在疾病进展期间，共感器使用开关在大约70％的感染个体中包括CXCR4。使用共受体的主要决定因素位于病毒包膜的V3环中。在这里，使用V3回路的超深度焦磷酸测序（UDPS）来研究在初次HIV感染（PHI）期间是否可能存在使用CXCR4的（X4）病毒少数群体。根据MT-2细胞培养测定法，研究了3名HIV人群中改变了共受体使用的患者。通过V3回路的UDPS分析从PHI收集的纵向收集的血浆样品（每位患者四至九个样品），直到切换共受体后。根据模板分子的可用性，从每个样品中获得279至32,094个读数。 UDPS分析表明，在PHI期间或显性表型转换之前，不存在转换后出现的X4病毒。另外，系统发育分析表明，X4群体起源于获得先前的仅R5样本后已进化的R5变异体。最后，在PHI期间发现了1-3个主要变体，这证明了感染是由一个或几个病毒颗粒建立的。

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