期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
卷 1838, 期 10, 页码 2662-2669出版社
ELSEVIER
DOI: 10.1016/j.bbamem.2014.07.007
关键词
Human immunodeficiency virus-1 (HIV-1); Supported lipid bilayer; Atomic force microscopy; Lipid domain; Neutralizing antibody
资金
- Center for Biomolecular and Tissue Engineering (Duke University)
- Structural Biology and Biophysics program (Duke University)
- Karlsruhe House of Young Scientists (Karlsruhe Institute of Technology)
- NIH/NIAID [AI102814-01]
- East Asia and Pacific Summer Institutes program [NSF 1108266]
- Australian Microscopy and Microanalysis Research Facility (AMMRF)
The rare, broadly neutralizing antibodies, 4E10 and 2F5, that target the HIV-1 membrane proximal external region also associate with HIV-1 membrane lipids as part of a required first-step in HIV-1 neutralization. HIV-1 virions have high concentration of cholesterol and sphingomyelin, which are able to organize into liquid-ordered domains (i.e., lipid rafts), and could influence the interaction of neutralizing antibodies with epitopes proximal to the membrane. The objective of this research is to understand how these lipid domains contribute to 2F5/4E10 membrane interactions and to antigen presentation in liposomal form of HIV-1 vaccines. To this end we have engineered biomimetic supported lipid bilayers and are able to use atomic force microscopy to visualize membrane domains, antigen clustering, and antibody-membrane interactions. Our results demonstrate that 2F5/4E10 do not interact with highly ordered gel and liquid-ordered domains and exclusively bind to a liquid-disordered lipid phase. This suggests that vaccine liposomes that contain key viral membrane components, such as high cholesterol content, may not be advantageous for 2F5/4E10 vaccine strategies. Rather, vaccine liposomes that primarily contain a liquid-disordered phase may be more likely to elicit production of lipid reactive, 2F5- and 4E10-like antibodies. (C) 2014 Elsevier B.V. All rights reserved.
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