Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease - indication of an evolving epidemic in West Africa
Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease - indication of an evolving epidemic in West Africa
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DOI：
10.1186/1742-4690-7-23
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发表时间：
2010-03-22
期刊：
影响因子：
3.3
通讯作者：
Medstrand, Patrik
中科院分区：
文献类型：
--
作者：
Esbjornsson, Joakim;Mansson, Fredrik;Medstrand, Patrik
背景资料：HIV-1是进化最快的病原体之一，其特征在于地理和遗传变异，这些变异已被分类为不同的亚型和循环重组形式（CRF）。在感染的早期，主要的辅助受体是CCR 5，但在疾病过程中，可能会出现使用CXCR 4的HIV-1人群。这与HIV-1亚型B的加速疾病进展相关。由于最近在抗逆转录病毒治疗中引入了辅助受体拮抗剂，HIV-1辅助受体嗜性的基本知识很重要，关于HIV-1 CXCR 4使用人群在晚期疾病中出现频率的亚型特异性差异需要进一步研究。为了研究使用CXCR 4的人群在HIV-1 A亚型和CRF02_AG晚期疾病中出现的频率，我们评估了这些亚型的重组病毒表型检测的准确性，并使用它来确定HIV-1血浆样本的辅助受体嗜性在几内亚比绍晚期疾病期间收集。我们还进行了基因型分析，并调查亚型特异性差异的外观CXCR 4的嗜性晚在diseases.Results：我们发现，重组病毒表型检测准确预测HIV-1的辅助受体嗜性亚型A和CRF02_AG。在研究期间（1997-2007），我们发现CRF02_AG中CXCR 4趋向性频率增加且普遍较高（86%）。通过对我们的样品的V3区的序列分析，我们开发了一种新的基因型规则，用于预测CRF02_AG中CXCR 4的嗜性，该规则基于带电荷氨基酸总数和净电荷的组合标准。该规则比先前描述的基因型规则具有更高的灵敏度，并且可能有助于开发本CRF的未来基因型工具。最后，我们进行了一项文献分析，结合498例晚期疾病患者的数据，发现除了C亚型（15%）外，所有主要HIV-1亚型（60-77%）的CXCR 4嗜性都很高。文献分析的结果表明，需要进一步的研究调查亚型特异性出现CXCR 4嗜性，这可能是特别重要的，由于在HIV治疗方案中引入CCR 5拮抗剂。
Background: HIV-1 is one of the fastest evolving pathogens, and is distinguished by geographic and genetic variants that have been classified into different subtypes and circulating recombinant forms (CRFs). Early in infection the primary coreceptor is CCR5, but during disease course CXCR4-using HIV-1 populations may emerge. This has been correlated with accelerated disease progression in HIV-1 subtype B. Basic knowledge of HIV-1 coreceptor tropism is important due to the recent introduction of coreceptor antagonists in antiretroviral therapy, and subtype-specific differences regarding how frequently HIV-1 CXCR4-using populations appear in late-stage disease need to be further investigated. To study how frequently CXCR4-using populations appear in late-stage disease among HIV-1 subtype A and CRF02_AG, we evaluated the accuracy of a recombinant virus phenotypic assay for these subtypes, and used it to determine the HIV-1 coreceptor tropism of plasma samples collected during late-stage disease in Guinea-Bissau. We also performed a genotypic analysis and investigated subtype-specific differences in the appearance of CXCR4 tropism late in disease.Results: We found that the recombinant virus phenotypic assay accurately predicted HIV-1 coreceptor tropism of subtype A and CRF02_AG. Over the study period (1997-2007), we found an increasing and generally high frequency of CXCR4 tropism (86%) in CRF02_AG. By sequence analysis of the V3 region of our samples we developed a novel genotypic rule for predicting CXCR4 tropism in CRF02_AG, based on the combined criteria of the total number of charged amino acids and net charge. This rule had higher sensitivity than previously described genotypic rules and may be useful for development of future genotypic tools for this CRF. Finally, we conducted a literature analysis, combining data of 498 individuals in late-stage disease, and found high amounts of CXCR4 tropism for all major HIV-1 subtypes (60-77%), except for subtype C (15%).Conclusions: The increase in CXCR4 tropism over time suggests an evolving epidemic of CRF02_AG. The results of the literature analysis demonstrate the need for further studies investigating subtype-specific emergence for CXCR4-tropism; this may be particularly important due to the introduction of CCR5-antagonists in HIV treatment regimens.