Rose Justine D, Rhea Ariel M, Weber Jan, Quiñones-Mateu Miguel E
Diagnostic HYBRIDS Inc, Cleveland, OH 44103, USA.
Curr Opin HIV AIDS. 2009 Mar;4(2):136-42. doi: 10.1097/COH.0b013e328322f973.
HIV-1 entry into target cells is a complex multistage process involving the envelope glycoprotein, primary cellular receptor CD4, and at least two main cellular coreceptors, CCR5 and CXCR4. The identification of the HIV-1 coreceptors led to the rapid development of several drug candidates that selectively block this interaction, that is, CCR5 or CXCR4 antagonists. Here, we review different methodologies used to determine the ability of the virus to use one or both coreceptors and their potential role in managing HIV-infected individuals treated with these novel drugs.
Most commercially available HIV-1 tropism assays are cell-based (phenotypic) tests, which use different methodologies to generate env-recombinant viruses and distinct detection systems. On the other hand, a large effort is being devoted to develop more robust bioinformatic (genotypic) tools that may expedite HIV-1 tropism assays without compromising their accuracy. The main goal, however, continues to be to improve the sensitivity to detect minor CXCR4-tropic variants within the in-vivo HIV-1 quasispecies.
An accurate determination, and perhaps quantification, of HIV-1 coreceptor usage is necessary for the successful management of HIV-infected individuals in the new era of entry inhibitors. Further studies, aimed to the development of novel methodologies, are essential for the success of this new class of drugs.
HIV-1进入靶细胞是一个复杂的多阶段过程，涉及包膜糖蛋白、主要细胞受体CD4以及至少两种主要细胞共受体CCR5和CXCR4。HIV-1共受体的鉴定促使迅速开发出几种选择性阻断这种相互作用的候选药物，即CCR5或CXCR4拮抗剂。在此，我们综述用于确定病毒使用一种或两种共受体能力的不同方法及其在管理接受这些新药治疗的HIV感染者中的潜在作用。
大多数市售的HIV-1嗜性检测是基于细胞的（表型）检测，其使用不同方法生成env重组病毒和不同的检测系统。另一方面，人们正在大力开发更强大的生物信息学（基因型）工具，这些工具可能会加快HIV-1嗜性检测，同时又不影响其准确性。然而，主要目标仍然是提高检测体内HIV-1准种中少量CXCR4嗜性变体的敏感性。
在进入抑制剂的新时代，准确测定（或许还包括定量）HIV-1共受体的使用情况对于成功管理HIV感染者至关重要。旨在开发新方法的进一步研究对于这类新药的成功至关重要。
