Wang W K, Lee C N, Dudek T, Chang S Y, Zhao Y J, Essex M, Lee T H
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
AIDS Res Hum Retroviruses. 2000 Nov 20;16(17):1821-9. doi: 10.1089/08892220050195784.
Several seven-transmembrane chemokine receptors are known to function as entry coreceptors for human immunodeficiency virus type 1. CCR5 and CXCR4 are the major coreceptors for non-syncytium-inducing (NSI) and syncytium-inducing (SI) viruses, respectively. During the natural course of infection, the emergence of variants with a phenotypic transition from NSI to SI and rapid disease progression is associated with expanded coreceptor usage to CXCR4. Characteristic amino acids at several positions in the hypervariable region 3 (V3) of gp120 have been linked to CXCR4 utilization. Previously, we reported that a highly conserved arginine residue of V3 played an important role in CCR5 utilization. In this study, the possible involvement of the same arginine residue in CXCR4 utilization was investigated. Amino acid substitutions introduced to this arginine on R5X4 viruses were found to have a significant effect on their utilization of CXCR4. These results, taken together with those reported previously, suggest that this highly conserved arginine may contribute to the functional convergence of chemokine coreceptor utilization by human immunodeficiency viruses and may represent a unique target for future antiviral design.
已知几种七跨膜趋化因子受体可作为1型人类免疫缺陷病毒的进入共受体发挥作用。CCR5和CXCR4分别是非合胞体诱导型（NSI）和合胞体诱导型（SI）病毒的主要共受体。在感染的自然病程中，表型从NSI转变为SI且疾病进展迅速的病毒变体的出现与共受体使用范围扩展至CXCR4有关。gp120高变区3（V3）中几个位置的特征性氨基酸与CXCR4的利用有关。此前，我们报道V3的一个高度保守的精氨酸残基在CCR5利用中起重要作用。在本研究中，调查了同一个精氨酸残基在CXCR4利用中可能的作用。发现在R5X4病毒上对该精氨酸进行的氨基酸替换对其CXCR4利用有显著影响。这些结果与先前报道的结果一起表明，这种高度保守的精氨酸可能有助于人类免疫缺陷病毒趋化因子共受体利用的功能趋同，并且可能代表未来抗病毒设计的一个独特靶点。
