Singh Ashika, Page Taryn, Moore Penny L, Allgaier Rachel L, Hiramen Keshni, Coovadia Hoosen M, Walker Bruce D, Morris Lynn, Ndung'u Thumbi
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
Virology. 2009 Oct 10;393(1):56-67. doi: 10.1016/j.virol.2009.07.021. Epub 2009 Aug 19.
It is widely documented that a complete switch from the predominant CCR5 (R5) to CXCR4 (X4) phenotype is less common for HIV-1 subtype C (HIV-1C) compared to other major subtypes. We investigated whether dualtropic HIV-1C isolates represented dualtropic, mixed R5 and X4 clones or both. Thirty of 35 functional HIV-1 env clones generated by bulk PCR amplification from peripheral blood mononuclear cells (PBMCs) infected with seven dualtropic HIV-1C isolates utilized CXCR4 exclusively. Five of 35 clones displayed dualtropism. Endpoint dilution of one isolate did not yield a substantial proportion of R5-monotropic env clones. Sequence-based predictive algorithms showed that env sequences from PBMCs, CXCR4 or CCR5-expressing cell lines were indistinguishable and all possessed X4/dualtropic characteristics. We describe HIV-1C CXCR4-tropic env sequence features. Our results suggest a dramatic loss of CCR5 monotropism as dualtropism emerges in HIV-1C which has important implications for the use of coreceptor antagonists in therapeutic strategies for this subtype.
有大量文献记载，与其他主要亚型相比，HIV-1 C型（HIV-1C）从主要的CCR5（R5）表型完全转变为CXCR4（X4）表型的情况较少见。我们研究了双嗜性HIV-1C分离株是代表双嗜性、混合的R5和X4克隆，还是两者皆有。通过批量PCR扩增从感染了7株双嗜性HIV-1C分离株的外周血单核细胞（PBMC）中产生的35个功能性HIV-1 env克隆中，有30个仅利用CXCR4。35个克隆中有5个显示出双嗜性。对一株分离株进行终点稀释未产生大量比例的R5单嗜性env克隆。基于序列的预测算法表明，来自PBMC、表达CXCR4或CCR5的细胞系的env序列无法区分，且均具有X4/双嗜性特征。我们描述了HIV-1C CXCR4嗜性env序列特征。我们的结果表明，在HIV-1C中出现双嗜性时，CCR5单嗜性会显著丧失，这对于在该亚型的治疗策略中使用共受体拮抗剂具有重要意义。
