@article{53871e5b098a4795a39662cc8662636f,
title = "Discovery of O-Linked Carbohydrate on HIV-1 Envelope and Its Role in Shielding against One Category of Broadly Neutralizing Antibodies",
abstract = "Approximately 50% of the mass of the Envelope (Env) glycoprotein surface subunit (gp120) of human immunodeficiency virus type 1 (HIV-1) is composed of N-linked carbohydrate. Until now, the dogma has been that HIV-1 lacks O-linked carbohydrate on Env. Here we show that a subset of patient-derived HIV-1 isolates contain O-linked carbohydrate on the variable 1 (V1) domain of Env gp120. We demonstrate the presence of this O-glycosylation both on virions and on gp120 expressed as a secreted protein. Further, we establish that these O-linked glycans can confer a more than 1,000-fold decrease in neutralization sensitivity (IC50) to V3-glycan broadly neutralizing antibodies. These findings uncover a structural modification to the HIV-1 Env and suggest a functional role in promoting viral escape from one category of broadly neutralizing antibodies.",
keywords = "Envelope, HIV-1, O-glycosylation, V1 domain, broadly neutralizing antibodies, escape mechanism, gp120, immune evasion",
author = "Silver, {Zachary A.} and Aristotelis Antonopoulos and Haslam, {Stuart M.} and Anne Dell and Dickinson, {Gordon M.} and Seaman, {Michael S.} and Desrosiers, {Ronald C.}",
note = "Funding Information: We thank D.G. Isom for his guidance in developing the Python program and H.J. Joshi for facilitating the acquisition of NetOGlyc4.0 O-glycosylation prediction data for our 4,757 HIV-1 Env sequences. We also thank W.A. Lauer and D.E. Mendes for assistance with the jacalin-binding ELISAs and S.P. Fuchs for providing key insights into the development of our research plan. Last but not least, we would like to acknowledge E.S. Church (Stansell), whose work set the foundation for this study. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under awards F30AI134381 (Z.A.S.) and R01AI104523 (R.C.D.) and by the Wellcome Trust (Senior Investigator Award to A.D.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: We thank D.G. Isom for his guidance in developing the Python program and H.J. Joshi for facilitating the acquisition of NetOGlyc4.0 O-glycosylation prediction data for our 4,757 HIV-1 Env sequences. We also thank W.A. Lauer and D.E. Mendes for assistance with the jacalin-binding ELISAs and S.P. Fuchs for providing key insights into the development of our research plan. Last but not least, we would like to acknowledge E.S. Church (Stansell), whose work set the foundation for this study. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under awards F30AI134381 (Z.A.S.) and R01AI104523 (R.C.D.) and by the Wellcome Trust (Senior Investigator Award to A.D.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Z.A.S. and R.C.D. conceived the idea. Z.A.S. wrote the Python computer algorithm, designed all plasmids, and was responsible for experimental design, execution, data analysis, and manuscript preparation. A.A. S.M.H. and A.D. performed and analyzed the mass spectrometry experiments. M.S.S. tested the recombinant viruses in neutralization assays. G.M.D. initiated the plans that led to this line of investigation. R.C.D. helped plan the experiments, supervised the research, interpreted the data, and contributed to the preparation of this manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = feb,
day = "11",
doi = "10.1016/j.celrep.2020.01.056",
language = "English (US)",
volume = "30",
pages = "1862--1869.e4",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}