Sato H, Kato K, Takebe Y
Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku, Tokyo, 162-8640, Japan.
Virology. 1999 May 10;257(2):491-501. doi: 10.1006/viro.1999.9670.
The hypervariable V3 loop within gp120 of human immunodeficiency virus type 1 (HIV-1) is the major determinant of cell tropism and the entry coreceptor usage of the virus. However, the information obtained thus far has been from only subtype B from North America and Europe, and little is known about other subtypes whose V3 amino acids differ by as much as 50% from subtype B V3. In this study, we examined the functional potential of the V3 element of the HIV-1 subtype E, the most crucial variant causing the AIDS epidemic throughout southeast Asia. A panel of HIV-1LAI recombinants was constructed by the overlap extension method, by which the LAI V3 loop was precisely replaced by that of the subtype E nonsyncytium-inducing (NSI) or syncytium-inducing (SI) variant. All of the recombinant viruses infected peripheral blood mononuclear cells, whereas only those with SI V3 infected MT2 cells, a CD4(+) T cell line. Consistently, the SI V3 recombinants used CXCR4, while the NSI V3 recombinants used CCR5 for infection of HOS-CD4(+) cells. Finally, only the NSI V3 sequence conferred CC-chemokine sensitivity on the parental virus. The data support the notion that the HIV-1 V3 loop consists of a relatively independent domain in gp120 and suggest that the subtype E V3 loop indeed contains the functional element to dictate the cell tropism, coreceptor preference, and chemokine sensitivity of the virus. These findings are of immediate importance in understanding V3 structure-function relationship and for examining phenotypic evolution of HIV-1 subtype E.
人类免疫缺陷病毒1型（HIV-1）的gp120内的高变V3环是细胞嗜性和病毒进入共受体使用的主要决定因素。然而，迄今为止所获得的信息仅来自北美和欧洲的B亚型，对于其他V3氨基酸与B亚型相差多达50%的亚型了解甚少。在本研究中，我们检测了HIV-1 E亚型V3元件的功能潜力，E亚型是在东南亚导致艾滋病流行的最关键变体。通过重叠延伸法构建了一组HIV-1 LAI重组体，通过该方法，LAI V3环被E亚型非融合诱导（NSI）或融合诱导（SI）变体的V3环精确取代。所有重组病毒都感染外周血单核细胞，而只有那些带有SI V3的病毒感染MT2细胞，MT2是一种CD4(+) T细胞系。一致地，SI V3重组体使用CXCR4，而NSI V3重组体使用CCR5来感染HOS-CD4(+)细胞。最后，只有NSI V3序列赋予亲本病毒对CC趋化因子的敏感性。这些数据支持了HIV-1 V3环在gp120中由一个相对独立的结构域组成的观点，并表明E亚型V3环确实包含决定病毒细胞嗜性、共受体偏好和趋化因子敏感性的功能元件。这些发现对于理解V3结构-功能关系以及研究HIV-1 E亚型的表型进化具有直接的重要意义。
