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Functional and genetic analysis of coreceptor usage by dualtropic HIV-1 subtype C isolates |
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| Authors: | Ashika Singh Penny L. Moore Keshni Hiramen Bruce D. Walker Lynn Morris |
| Affiliation: | a HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa b AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa c Ragon Institute of MGH, MIT and Harvard, Charlestown, MA, USA d Department of Paediatrics and Child Heath, Nelson R. Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa |
| Abstract: | 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. |
| Keywords: | HIV-1 subtype C Dualtropism Coreceptor usage Envelope V3 loop CXCR4 |
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