title: Amino- and Carboxyl-Terminal CCR5 Mutations in Brazilian HIV-1-Infected Women and Homology Model of p.L55Q CCR5 Mutant.
abstract: Genetic factors from an HIV-1 host can affect the rate of progression to AIDS and HIV infection. To investigate the frequency of mutations in the CCR5 gene, HIV-1 samples from infected women and uninfected individuals were selected for sequencing of the CCR5 gene regions encoding the N- and C-terminal protein domains. Physicochemical CCR5 modeling and potential protein domain analysis were performed in order to evaluate the impact of the mutations found in the properties and structure of CCR5. The p.L55Q mutation in the N-terminal protein domain was observed only in uninfected individuals, with an allelic frequency of 1.8%. Physicochemical analysis revealed that the p.L55Q mutation magnified the flexibility and accessibility profiles and the modeling of CCR5 structures showed resulting in a small deviation to the right, as well as a hydrophobic to hydrophilic property alteration. The p.L55Q mutation also resulted in a slight modification of the electrostatic load of this region. Additionally, three novel silent mutations were found at the C-terminal coding region among HIV-1-infected women. The results suggest that the p.L55Q mutation might alter CCR5 conformation. Further studies should be conducted to verify the role of this mutation in HIV-1 susceptibility.
authors.affiliation: 1 Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz , Salvador, Bahia, Brazil .|2 Universidade Federal da Bahia , Salvador, Bahia, Brazil .
authors.forename: Giselle Calasans de Souza
authors.initials: GC
authors.lastname: Costa
authors.affiliation: 3 Bioinformatic Core, Center for Technological Innovation, Evandro Chagas Institute , Pará, Brazil .
authors.forename: Marcio Roberto T
authors.initials: MR
authors.lastname: Nunes
authors.affiliation: 1 Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz , Salvador, Bahia, Brazil .
authors.forename: Jaqueline Goes
authors.initials: JG
authors.lastname: Jesus
authors.affiliation: 1 Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz , Salvador, Bahia, Brazil .
authors.forename: Thiago
authors.initials: T
authors.lastname: Novaes
authors.affiliation: 3 Bioinformatic Core, Center for Technological Innovation, Evandro Chagas Institute , Pará, Brazil .
authors.forename: Jedson Ferreira
authors.initials: JF
authors.lastname: Cardoso
authors.affiliation: 3 Bioinformatic Core, Center for Technological Innovation, Evandro Chagas Institute , Pará, Brazil .
authors.forename: Edivaldo Costa
authors.initials: EC
authors.lastname: Sousa Júnior
authors.affiliation: 1 Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz , Salvador, Bahia, Brazil .
authors.forename: Edson de Souza
authors.initials: Ede S
authors.lastname: Santos
authors.affiliation: 1 Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz , Salvador, Bahia, Brazil .
authors.forename: Bernardo
authors.initials: B
authors.lastname: Galvão-Castro
authors.affiliation: 1 Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz , Salvador, Bahia, Brazil .
authors.forename: Dalila Luciola
authors.initials: DL
authors.lastname: Zanette
authors.affiliation: 1 Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz , Salvador, Bahia, Brazil .|2 Universidade Federal da Bahia , Salvador, Bahia, Brazil .
authors.forename: Marilda de Souza
authors.initials: Mde S
authors.lastname: Gonçalves
authors.affiliation: 1 Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz , Salvador, Bahia, Brazil .
authors.forename: Luiz Carlos Junior
authors.initials: LC
authors.lastname: Alcantara
mesh_terms: D000328:Adult; D000368:Aged; D001938:Brazil; D055598:Chemical Phenomena; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics*; D009154:Mutation; D011487:Protein Conformation; D019713:Receptors, CCR5 / Q000737:chemistry / Q000235:genetics*; D015728:Receptors, HIV / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
chemical_list: C584933:CCR5 protein, human; D050505:Mutant Proteins; D019713:Receptors, CCR5; D015728:Receptors, HIV