Functional and genetic analysis of coreceptor usage by dualtropic HIV-1 subtype C isolates.
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.
Singh
Ashika
A
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
Page
Taryn
T
Moore
Penny L
PL
Allgaier
Rachel L
RL
Hiramen
Keshni
K
Coovadia
Hoosen M
HM
Walker
Bruce D
BD
Morris
Lynn
L
Ndung'u
Thumbi
T
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000379:methods; D019713:Receptors, CCR5 / Q000032:analysis; D054380:Receptors, CXCR5 / Q000032:analysis; D015728:Receptors, HIV / Q000032:analysis* / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D053586:Virus Internalization; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
C095085:CXCR5 protein, human; D004279:DNA, Viral; D019713:Receptors, CCR5; D054380:Receptors, CXCR5; D015728:Receptors, HIV; D054299:env Gene Products, Human Immunodeficiency Virus
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