Abstract

Recognition of cell-surface receptors and co-receptors is a crucial molecular event towards the establishment of HIV infection. HIV exists as several variants that differentially recognize the principal co-receptors, CCR5 and CXCR4, in different cell types, known as HIV co-receptor-tropism. The relative levels of these variants dynamically adjust to the changing host selection pressures to infect a vast repertoire of cells in a stage-specific manner. HIV infection sets in through immune cells such as dendritic cells, macrophages, and T-lymphocytes in the acute stage, while a wide range of other cells, including astrocytes, glial cells, B-lymphocytes, and epithelial cells, are infected during chronic stages. A change in tropism occurs during the transition from acute to a chronic phase, termed as co-receptor switching marked by a change in disease severity. The cellular and molecular events leading to co-receptor switching are poorly understood. This review aims to collate our present understanding of the dynamics of HIV co-receptor-tropism vis-à-vis host and viral factors, highlighting the cellular and molecular events involved therein. We present the possible correlations between virus entry, cell tropism, and co-receptor switching, speculating its consequences on disease progression, and proposing new scientific pursuits to help in an in-depth understanding of HIV biology.

摘要

识别细胞表面受体和共受体是建立 HIV 感染的关键分子事件。HIV 以几种变体形式存在，这些变体在不同细胞类型中区别识别主要的共同受体 CCR5 和 CXCR4，称为 HIV 共同受体向性。这些变体的相对水平会随着宿主选择压力的变化而动态调整，从而以特定于阶段的方式感染大量细胞。HIV 感染在急性期通过树突状细胞、巨噬细胞和 T 淋巴细胞等免疫细胞发生，而在慢性期感染大量其他细胞，包括星形胶质细胞、神经胶质细胞、B 淋巴细胞和上皮细胞. 向性的变化发生在从急性期到慢性期的过渡期间，称为以疾病严重程度变化为标志的共受体转换。导致共同受体转换的细胞和分子事件知之甚少。本综述旨在整理我们目前对 HIV 共受体向性相对于宿主和病毒因子的动态的理解，重点介绍其中涉及的细胞和分子事件。我们介绍了病毒进入、细胞趋向性和共受体转换之间可能的相关性，推测其对疾病进展的影响，并提出新的科学追求以帮助深入了解 HIV 生物学。突出其中涉及的细胞和分子事件。我们介绍了病毒进入、细胞趋向性和共受体转换之间可能的相关性，推测其对疾病进展的影响，并提出新的科学追求以帮助深入了解 HIV 生物学。突出其中涉及的细胞和分子事件。我们介绍了病毒进入、细胞趋向性和共受体转换之间可能的相关性，推测其对疾病进展的影响，并提出新的科学追求以帮助深入了解 HIV 生物学。