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HIV-1 envelope subregion length variation during disease progression.
Title | HIV-1 envelope subregion length variation during disease progression. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Curlin, ME, Zioni, R, Hawes, SE, Liu, Y, Deng, W, Gottlieb, GS, Zhu, T, Mullins, JI |
Journal | PLoS Pathog |
Volume | 6 |
Issue | 12 |
Pagination | e1001228 |
Date Published | 2010 |
ISSN | 1553-7374 |
Keywords | Cross-Sectional Studies, Disease Progression, HIV Envelope Protein gp120, HIV Infections, HIV-1, Host-Pathogen Interactions, Humans, Immune Evasion, Pandemics |
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. |
DOI | 10.1371/journal.ppat.1001228 |
Alternate Journal | PLoS Pathog. |
PubMed ID | 21187897 |