title: Evidences for viral strain selection in late stages of HIV infection: an analysis of Vpu alleles.
abstract: One of the most studied topics about AIDS disease is the presence of different progression levels in patients infected by HIV. Several studies have shown that this progression is directly associated with host genetics, although viral factors are also known to play a role. Here we explore the contribution of Vpu protein in the evolution of viral population. The sequence variation of Vpu was analyzed during HIV infection in peripheral blood monocyte cells of 12 patients in different clinical stages of HIV-1 infection early and late stages of infections, separated by at least 4 years. The clustering analysis of Vpu sequences showed higher diversity of early alleles, non-random distribution of sequences, and viral evolution strains selection. Forty-two amino acid modifications were found in the multiple alignments of the 57 different alleles found for early stage were 23 modifications were found in the late stage dataset. Interestingly fourteen alteration of early stage were located in conserved site related with Vpu functions alterations while these alterations appear with less frequency in the late stage of infection. Moreover, late stage alleles tend to be similar with the Vpu wild type sequence, suggesting viral selection toward populations harboring more efficient variants during the course of infection. This would contribute to higher infectivity and viral replication actually observed at the aggressive late stages of infection. These data, in conjunction with in vitro experiments, will be important to elucidation of the physiological relevance of Vpu protein in the pathogenic mechanisms of AIDS.
authors.affiliation: Laboratory of Molecular Virology, Faculty of Health Science, University of Brasilia, Brasilia, DF, Brazil.
authors.forename: Marcos Vinícius Pereira
authors.initials: MV
authors.lastname: Gondim
authors.forename: Joaquim Xavier
authors.initials: JX
authors.lastname: da Silva
authors.forename: Francisco
authors.initials: F
authors.lastname: Prosdocimi
authors.forename: Eduardo
authors.initials: E
authors.lastname: Leonardecz-Neto
authors.forename: Octávio Luiz
authors.initials: OL
authors.lastname: Franco
authors.forename: Enrique Roberto
authors.initials: ER
authors.lastname: Argañaraz
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D015331:Cohort Studies; D018450:Disease Progression; D015658:HIV Infections / Q000097:blood / Q000503:physiopathology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008404:Massachusetts; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000821:virology; D012641:Selection, Genetic; D016415:Sequence Alignment; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult; D000086082:Viroporin Proteins
chemical_list: D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins