title: Charged amino acid patterns of coreceptor use in the major subtypes of human immunodeficiency virus type 1.
abstract: Human immunodeficiency virus type 1 has several genetic subtypes and two coreceptor use phenotypes: R5 that uses CCR5, while X4 uses CXCR4. A high amino acid charge of the envelope glycoprotein 120 V3 region, common at positions 11 and 25, is important for CXCR4 use. We characterized charged V3 amino acids, retrieving all biologically phenotyped sequences from the HIV Sequence Database. Selecting individually unique ones randomly yielded 48 subtype A, 231 B, 180 C, 37 D and 32 CRF01_AE sequences; 482 were R5 and 46 were X4. Charged amino acids were conserved in both R5 and X4 with general and subtype-specific patterns. X4 viruses gained a higher charge from positive amino acids at positions other than in R5, and through the loss of negative amino acids. Other positions than 11/25 had a greater impact on charge (P<0.001). This describes how R5 evolves into X4 in a subtype-specific context, useful for computer-based predictions and vaccine design.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, PO Box 280, SE-171 77 Stockholm, Sweden.
authors.forename: Lotta
authors.initials: L
authors.lastname: Pramanik
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, PO Box 280, SE-171 77 Stockholm, Sweden.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Fried
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, PO Box 280, SE-171 77 Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Clevestig
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, PO Box 280, SE-171 77 Stockholm, Sweden.
authors.forename: Anneka
authors.initials: A
authors.lastname: Ehrnst
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D024361:Amino Acids, Basic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013045:Species Specificity
chemical_list: D024361:Amino Acids, Basic; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV