M嗜性HIV-1毒株一过性感染T细胞系的研究

目的了解早期分离毒株一过性感染Ｔ细胞的分子机制。方法将毒株在Ｔ细胞系培养后，在观察其生物学性状的同时，对外膜基因进行序列分析，确定毒株的基因变异，并结合异源双链泳动分析，了解病毒群的复杂度。结果序列分析显示这些病毒都是Ｍ嗜性、非介导融合型（ＮＳＩ），与其生物学性状一致；在Ｔ细胞系传代过程中发生较大变异，都在不同程度上表现出偏离Ｍ嗜性、ＮＳＩ的序列特征；尽管有一毒株（编号：ＣＮ９７００１）在末代序列中已有介导融合型（ＳＩ）的特征，但却未能显示ＳＩ的表型。异源双链泳动分析显示，病毒群复杂度在传代刚开始时低，以后一直较高。结论结果提示，Ｍ嗜性、ＮＳＩ毒株为适应Ｔ细胞系，向不同变异方向作了尝试，但都未成功。虽然ＨＩＶ外膜基因与毒株的细胞嗜性、受体使用，与介导融合等特性有关，但这些表型的体现与否，还与毒株的整个基因组背景有关。在早期感染的Ｍ嗜性、ＮＳＩ毒株群中并没有Ｔ嗜性／ＳＩ毒株存在，是后来在体内随感染延续而产生的。

Study on transient infection of T cell lines by M tropic HIV1 strains

Objective To reveal the mechanism of transient infection of T cell by HIV1 isolates of early stages from Yunnan and Xinjiang, China. Methods we made these viruses pass on CXCR4 expressing T cell lines and CCR5 expressing U937 cell line. After having observed the biological phenotype, we analyzed sequences of env gene to find genetic mutations of the strains, and used heteroduplex mobility assay (HMA) to show the complexity of the virus groups. Results Sequence analysis indicated that these viruses are M tropic, NSI strains, correlating with their phenotype; they mutated largely through T cell passage, all showed sequence characteristics deviating from M tropic/NSI to different extents. HMA results indicated the complexity of virus groups was low at the very beginning of the passage and kept high later. Conclusion We concluded that these viruses tried mutating to different directions to adapt the T cell line but all failed. Although env gene correlates with cell tropism, coreceptor usage and HIV syncytium inducing, it may have relationship with the whole genome, whether these phenotypes are present or not. The results imply that there is no T tropic/SI strain in the M topic/NSI virus pool in early infection, it is generated later following continued infection in vivo.