HIV-1 Envelope Subregion Length Variation during Disease Progression

PLoS Pathogens

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