PLoS Pathogens | |
HIV-1 Envelope Subregion Length Variation during Disease Progression | |
Stephen E. Hawes1  Rafael Zioni2  Tuofu Zhu2  Marcel E. Curlin3  Geoffrey S. Gottlieb3  Wenjie Deng4  James I. Mullins4  Yi Liu4  | |
[1] Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, United States of America;Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America;Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America;Department of Microbiology, University of Washington School of Medicine, Seattle, Washington, United States of America | |
关键词: Glycosylation; Sequence analysis; HIV-1; Coreceptors; HIV; Viral load; AIDS; Immune response; | |
DOI : 10.1371/journal.ppat.1001228 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201902012549278ZK.pdf | 1601KB | download |