Zhang Y J, Zhang L, Ketas T, Korber B T, Moore J P
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York, USA.
AIDS Res Hum Retroviruses. 2001 Feb 10;17(3):217-27. doi: 10.1089/088922201750063133.
We describe the cloning of env genes from the mother-infant HIV-1 isolate pair P6-v3 and M6-v3. These viruses are unusual in that they can use the coreceptor Bonzo/STRL33 as well as CCR5 and, in the case of M6, CXCR4, to enter transfected cell lines in vitro. The phenotype of the parental isolates is generally reflected by the properties of the cloned env genes, when these are used in an Env-complementation assay of virus entry. Chimeric viruses were also made that contain the env genes of P6-v3 and M6-v3 inserted into the background of the infectious molecular clone, HIV-1 NL4-3. Some of the chimeric viruses derived from HIV1 P6-v3 were able to use Bonzo for entry into transfected cell lines, albeit to a lesser extent than they could use CCR5. There are some indications that one of these chimeric viruses, P6-v3-22-1, can use a coreceptor other than CCR5, perhaps Bonzo, to enter mitogen-stimulated PBMC, although only weakly. However, formal proof that this virus can use Bonzo in primary cells has not been obtained. The P6-v3-22-1 chimeric virus was unable to infect CD4-negative, placental cell lines, in the presence or absence of soluble CD4. Env sequence analysis revealed several differences among viruses with different tropisms, most notably a four amino acid deletion in the central region of the V3 loop that distinguishes the R5 virus P6-v3-25-4 from the R5, Bonzo virus P6-v3-22-1.
我们描述了从母婴HIV-1分离株对P6-v3和M6-v3中克隆env基因的过程。这些病毒不同寻常之处在于,它们在体外能够利用共受体Bonzo/STRL33以及CCR5,对于M6病毒而言,还能利用CXCR4进入转染的细胞系。当在病毒进入的Env互补试验中使用这些克隆的env基因时,亲代分离株的表型通常由其特性反映出来。还构建了嵌合病毒,它们含有插入到感染性分子克隆HIV-1 NL4-3背景中的P6-v3和M6-v3的env基因。一些源自HIV1 P6-v3的嵌合病毒能够利用Bonzo进入转染的细胞系,尽管其程度低于利用CCR5的程度。有迹象表明,这些嵌合病毒之一,即P6-v3-22-1,能够利用除CCR5之外的共受体(可能是Bonzo)进入丝裂原刺激的外周血单核细胞(PBMC),尽管效率很低。然而,尚未获得该病毒能够在原代细胞中利用Bonzo的正式证据。在有或没有可溶性CD4的情况下,P6-v3-22-1嵌合病毒均无法感染CD4阴性的胎盘细胞系。Env序列分析揭示了具有不同嗜性的病毒之间的几个差异,最显著的是V3环中央区域的四个氨基酸缺失,这使得R5病毒P6-v3-25-4与R5、Bonzo病毒P6-v3-22-1区分开来。