title: Purifying selection of CCR5-tropic human immunodeficiency virus type 1 variants in AIDS subjects that have developed syncytium-inducing, CXCR4-tropic viruses.
abstract: Human immunodeficiency virus type 1 (HIV-1) infection is established by virus variants that use the CCR5 co-receptor for entry (CCR5-tropic or R5 variants), whereas viruses that use CXCR4 as co-receptor (CXCR4-tropic or X4 variants) emerge during disease progression in approximately 50 % of infected subjects. X4 variants may have a higher fitness ex vivo and their detection is usually accompanied by faster T-cell depletion and the onset of AIDS in HIV-1-positive individuals. Here, the relationship between the sequence variation of the HIV-1 env V3-V5 region and positive selective pressure on R5 and X4 variants from infected subjects with CD4 T cell counts below 200 cells microl(-1) was studied. A correlation was found between genetic distance and CD4(+) cell count at late stages of the disease. R5 variants that co-existed with X4 variants were significantly less heterogeneous than R5 variants from subjects without X4 variants (P < 0.0001). Similarly, X4 variants had a significantly higher diversity than R5 variants (P < 0.0001), although residues under positive selection had a similar distribution pattern in both variants. Therefore, both X4 and R5 variants were subjected to high selective pressures from the host. Furthermore, the interaction between X4 and R5 variants within the same subject resulted in a purifying selection on R5 variants, which only survived as a homogeneous virus population. These results indicate that R5 variants from X4 phenotype samples were highly homogeneous and under weakly positive selective pressures. In contrast, R5 variants from R5 phenotype samples were highly heterogeneous and subject to positive selective pressures.
authors.affiliation: Fundacio irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), 08916 Badalona, Spain.
authors.forename: Guerau
authors.initials: G
authors.lastname: Fernàndez
authors.affiliation: Fundacio irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), 08916 Badalona, Spain.
authors.forename: Anuska
authors.initials: A
authors.lastname: Llano
authors.affiliation: Fundacio irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), 08916 Badalona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Esgleas
authors.affiliation: Fundacio irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), 08916 Badalona, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.affiliation: Fundacio irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), 08916 Badalona, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Esté
authors.affiliation: Fundacio irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), 08916 Badalona, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Martínez
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4