Soulié Cathia, Tubiana Roland, Simon Anne, Lambert-Niclot Sidonie, Malet Isabelle, Canestri Ana, Brunet Christel, Murphy Robert, Katlama Christine, Calvez Vincent, Marcelin Anne-Geneviève
Université Pierre et Marie Curie-Paris 6, UMR S-943 Paris, F-75013 France.
J Acquir Immune Defic Syndr. 2009 May 1;51(1):60-4. doi: 10.1097/QAI.0b013e31819fb903.
HIV-1 viruses have the ability to use CCR5 or CXCR4 coreceptors either solely (R5 or X4) or in combination (R5X4). The CCR5 antagonists block HIV entry into the cell and are specifically active against HIV-1 R5 strains. The objectives of this study were to investigate the predicted tropism of viruses present in paired cerebrospinal fluid (CSF) and plasma in a group of 22 HIV-1-infected patients with neurological disorders and to search for eventual discordance of predicted virus tropism between both compartments.
Paired CSF and plasma samples were selected from subjects harboring neurological disorders. V3 env was amplified and bulk sequenced, and HIV-1 coreceptor usage was determined from the V3 env region sequence by Geno2Pheno and position-specific scoring matrices (PSSM) algorithms.
The majority of subjects (19 of 22) had concordant virus predicted tropism in both compartments. All patients having R5-tropic viruses in plasma had R5-tropic viruses in CSF (17 of 22). Patients having R5X4/X4-tropic viruses in plasma could have R5X4/X4-using (2 of 22) or R5-tropic viruses (3 of 22) in CSF. The case of R5-tropic viruses in plasma and R5X4/X4-tropic viruses in CSF was never observed.
The majority of these patients have R5-using viruses in CSF that is mainly concordant with the predicted tropism in plasma. However, R5X4/X4 tropism in plasma does not necessarily mean the same predicted tropism in CSF compartment. Then, clinical therapeutic trials testing the clinical response to the CCR5 antagonists in patients with neurological disorders could be envisaged to analyze the effects of this therapeutic class in this setting.
HIV-1病毒能够单独使用CCR5或CXCR4共受体（R5或X4），也可以联合使用（R5X4）。CCR5拮抗剂可阻止HIV进入细胞，并且对HIV-1 R5毒株具有特异性活性。本研究的目的是调查22例患有神经系统疾病的HIV-1感染患者配对脑脊液（CSF）和血浆中病毒的预测嗜性，并寻找两个区室之间预测病毒嗜性的最终不一致情况。
从患有神经系统疾病的受试者中选取配对的CSF和血浆样本。扩增V3 env并进行高通量测序，通过Geno2Pheno和位置特异性评分矩阵（PSSM）算法从V3 env区域序列确定HIV-1共受体使用情况。
大多数受试者（22例中的19例）在两个区室中的病毒预测嗜性一致。血浆中具有R5嗜性病毒的所有患者脑脊液中也有R5嗜性病毒（22例中的17例）。血浆中具有R5X4/X4嗜性病毒的患者脑脊液中可能有使用R5X4/X4的病毒（22例中的2例）或R5嗜性病毒（22例中的3例）。从未观察到血浆中为R5嗜性病毒而脑脊液中为R5X4/X4嗜性病毒的情况。
这些患者中的大多数脑脊液中有使用R5的病毒，这与血浆中的预测嗜性基本一致。然而，血浆中的R5X4/X4嗜性并不一定意味着脑脊液区室中有相同的预测嗜性。因此，可以设想在患有神经系统疾病的患者中进行测试CCR5拮抗剂临床反应的临床治疗试验，以分析该治疗类别在这种情况下的效果。
