title: Human immunodeficiency virus type 1 gp120 envelope characteristics associated with disease progression differ in family members infected with genetically similar viruses.
abstract: The human immunodeficiency virus type 1 (HIV-1) envelope protein provides the primary contact between the virus and host, and is the main target of the adaptive humoral immune response. The length of gp120 variable loops and the number of N-linked glycosylation events are key determinants for virus infectivity and immune escape, while the V3 loop overall positive charge is known to affect co-receptor tropism. We selected two families in which both parents and two children had been infected with HIV-1 for nearly 10 years, but who demonstrated variable parameters of disease progression. We analysed the gp120 envelope sequence and compared individuals that progressed to those that did not in order to decipher evolutionary alterations that are associated with disease progression when individuals are infected with genetically related virus strains. The analysis of the V3-positive charge demonstrated an association between higher V3-positive charges with disease progression. The ratio between the amino acid length and the number of potential N-linked glycosylation sites was also shown to be associated with disease progression with the healthier family members having a lower ratio. In conclusion in individuals initially infected with genetically linked virus strains the V3-positive charges and N-linked glycosylation are associated with HIV-1 disease progression and follow varied evolutionary paths for individuals with varied disease progression.
authors.affiliation: Laboratory of Experimental Virology (LEV), Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Elly
authors.initials: E
authors.lastname: Baan
authors.affiliation: Laboratory of Experimental Virology (LEV), Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Renée M
authors.initials: RM
authors.lastname: van der Sluis
authors.affiliation: Laboratory of Experimental Virology (LEV), Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Margreet E
authors.initials: ME
authors.lastname: Bakker
authors.affiliation: Emma Children's Hospital, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bekker
authors.affiliation: Emma Children's Hospital, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Dasja
authors.initials: D
authors.lastname: Pajkrt
authors.affiliation: Clinical Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jurriaans
authors.affiliation: Emma Children's Hospital, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.affiliation: Laboratory of Experimental Virology (LEV), Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.affiliation: Clinical Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Katja C
authors.initials: KC
authors.lastname: Wolthers
authors.affiliation: Laboratory of Experimental Virology (LEV), Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: William A
authors.initials: WA
authors.lastname: Paxton
authors.affiliation: Laboratory of Experimental Virology (LEV), Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Georgios
authors.initials: G
authors.lastname: Pollakis
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002675:Child, Preschool; D058893:DNA Barcoding, Taxonomic / Q000379:methods; D018450:Disease Progression; D005190:Family; D005260:Female; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000596:Amino Acids; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral