Extreme Genetic Divergence Is Required for Coreceptor Switching in HIV-1 Subtype C

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 56; no. 1; pp. 9 - 15
• Main Authors: Coetzer, Mia, Nedellec, Rebecca, Cilliers, Tonie, Meyers, Tammy, Morris, Lynn, Mosier, Donald E
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-01-2011; Lippincott Williams & Wilkins; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Biological and medical sciences; Child; Cloning, Molecular; env Gene Products, Human Immunodeficiency Virus - genetics; Evolution; Fundamental and applied biological sciences. Psychology; Genetics; Genotype & phenotype; HIV; HIV Infections - immunology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Medical sciences; Microbiology; Miscellaneous; Molecular Sequence Data; Mutation; Phenotype; Phylogeny; Receptors, CCR5 - genetics; Receptors, CCR5 - immunology; Receptors, CXCR4 - genetics; Receptors, CXCR4 - immunology; Receptors, Formyl Peptide - genetics; Receptors, Formyl Peptide - immunology; Receptors, Lipoxin - genetics; Receptors, Lipoxin - immunology; Recombination, Genetic - genetics; Viral diseases; Virology; Virus; V1/V2 region; HIV-1 virus; HIV-1 subtype C; alternative coreceptors; Retroviridae; Genetics; Human immunodeficiency virus; coreceptor switching; Lentivirus; Subtype
• ISSN: 1525-4135; 1944-7884
• DOI: 10.1097/QAI.0b013e3181f63906

BACKGROUND:Coreceptor switching from CCR5 to CXCR4 is less common in subtype C HIV-1 infection than in subtype B for reasons that are unclear. We have examined sequential virus samples from a subtype C-infected child who had evidence of coreceptor switching.
METHODS:To examine HIV-1 envelope evolution towards CXCR4 usage, env sequences were correlated with phenotypic characteristics determined by entry assays, as well as the ability to use alternative coreceptors such as FPRL1, CCR3, CCR8 and others. The value of a phenotype predictor based on V3 sequences was also assessed.
RESULTS:Ninety-three sequences revealed 3 distinct coexistent virus lineages and only some members of one lineage evolved to use CXCR4. These lineages also had diverse alternative coreceptor patterns including the ability to use FPRL1, CCR3, CCR8, APJ, CMKLR1, RDC-1, CXCR6, CCR1, GPCR1, GPR15 and CCR6. Coreceptor switching was associated with extensive and rapid sequence divergence in the V1/V2 region in addition to V3 changes. Furthermore, interlineage recombination within the C2 region resulted in low predictability of a V3 sequence-based phenotype algorithm, and highlighted the importance of V1/V2 and V3 sequences in coreceptor usage.
CONCLUSION:These results suggest that the evolution to coreceptor switching in subtype C infection requires more mutations than other subtypes, and this contributes to the reduced incidence of R5X4 viruses.