title: HIV-1 envelope subregion length variation during disease progression.
abstract: The V3 loop of the HIV-1 Env protein is the primary determinant of viral coreceptor usage, whereas the V1V2 loop region is thought to influence coreceptor binding and participate in shielding of neutralization-sensitive regions of the Env glycoprotein gp120 from antibody responses. The functional properties and antigenicity of V1V2 are influenced by changes in amino acid sequence, sequence length and patterns of N-linked glycosylation. However, how these polymorphisms relate to HIV pathogenesis is not fully understood. We examined 5185 HIV-1 gp120 nucleotide sequence fragments and clinical data from 154 individuals (152 were infected with HIV-1 Subtype B). Sequences were aligned, translated, manually edited and separated into V1V2, C2, V3, C3, V4, C4 and V5 subregions. V1-V5 and subregion lengths were calculated, and potential N-linked glycosylation sites (PNLGS) counted. Loop lengths and PNLGS were examined as a function of time since infection, CD4 count, viral load, and calendar year in cross-sectional and longitudinal analyses. V1V2 length and PNLGS increased significantly through chronic infection before declining in late-stage infection. In cross-sectional analyses, V1V2 length also increased by calendar year between 1984 and 2004 in subjects with early and mid-stage illness. Our observations suggest that there is little selection for loop length at the time of transmission; following infection, HIV-1 adapts to host immune responses through increased V1V2 length and/or addition of carbohydrate moieties at N-linked glycosylation sites. V1V2 shortening during early and late-stage infection may reflect ineffective host immunity. Transmission from donors with chronic illness may have caused the modest increase in V1V2 length observed during the course of the pandemic.
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America. cemarcel@u.washington.edu
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Curlin
authors.forename: Rafael
authors.initials: R
authors.lastname: Zioni
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Hawes
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenjie
authors.initials: W
authors.lastname: Deng
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Gottlieb
authors.forename: Tuofu
authors.initials: T
authors.lastname: Zhu
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
mesh_terms: D003430:Cross-Sectional Studies; D018450:Disease Progression; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015658:HIV Infections / Q000453:epidemiology / Q000635:transmission*; D015497:HIV-1 / Q000737:chemistry / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D058873:Pandemics
chemical_list: D015699:HIV Envelope Protein gp120