Department of Biochemistry, University of Hyderabad, Hyderabad, India.
Crit Rev Microbiol. 2021 Aug;47(4):499-516. doi: 10.1080/1040841X.2021.1902941. Epub 2021 Apr 26.
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.
细胞表面受体和共受体的识别是 HIV 感染建立的关键分子事件。HIV 存在多种变体，这些变体在不同细胞类型中以不同的方式识别主要共受体 CCR5 和 CXCR4，这种差异被称为 HIV 共受体嗜性。这些变体的相对水平会动态调整，以适应宿主选择压力的变化，从而以特定于阶段的方式感染大量细胞。HIV 感染始于急性阶段的树突状细胞、巨噬细胞和 T 淋巴细胞等免疫细胞，而在慢性阶段，广泛的其他细胞，包括星形胶质细胞、神经胶质细胞、B 淋巴细胞和上皮细胞，也会被感染。在从急性到慢性阶段的转变过程中，会发生嗜性改变，称为共受体转换，其标志是疾病严重程度的变化。共受体转换的细胞和分子事件尚未完全了解。本综述旨在汇总我们目前对 HIV 共受体嗜性与宿主和病毒因素之间动态关系的理解，重点介绍其中涉及的细胞和分子事件。我们提出了病毒进入、细胞嗜性和共受体转换之间可能存在的相关性，推测其对疾病进展的影响，并提出新的科学研究方向，以帮助深入了解 HIV 生物学。
