Abstract

HIV-1 Env is a primary target for antibodies elicited during infection. Although a small number of infected individuals elicit broadly neutralizing antibodies, the bulk of humoral response consists of antibodies that do not neutralize or do so with limited breadth and effect protection through Fc receptor-dependent processes, such as antibody-dependent cellular cytotoxicity (ADCC). We have used X-ray crystallography as the primary means for understanding Env mechanism of immune evasion, and in 2014 published the first full atomic-level structure of the pre-fusion closed HIV-1 Env trimer. This structure reveals gp41 conformational changes, location of sequence variation, and details of the glycan shield. We are trying to build on this atomic-level information to gain comprehensive insight into how HIV-1 Env evades neutralizing antibody.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI005023-14
Application #
9161753
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
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State
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  Publications

Ma, Xiaochu; Lu, Maolin; Gorman, Jason et al. (2018) HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations. Elife 7:
Herschhorn, Alon; Gu, Christopher; Moraca, Francesca et al. (2017) The ?20-?21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions. Nat Commun 8:1049
Liu, Qingbo; Acharya, Priyamvada; Dolan, Michael A et al. (2017) Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer. Nat Struct Mol Biol 24:370-378
Lemmin, Thomas; Soto, Cinque; Stuckey, Jonathan et al. (2017) Microsecond Dynamics and Network Analysis of the HIV-1 SOSIP Env Trimer Reveal Collective Behavior and Conserved Microdomains of the Glycan Shield. Structure 25:1631-1639.e2
Shahzad-Ul-Hussan, Syed; Sastry, Mallika; Lemmin, Thomas et al. (2017) Insights from NMR Spectroscopy into the Conformational Properties of Man-9 and Its Recognition by Two HIV Binding Proteins. Chembiochem 18:764-771
Zhou, Tongqing; Doria-Rose, Nicole A; Cheng, Cheng et al. (2017) Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation. Cell Rep 19:719-732
Cheng, Cheng; Pancera, Marie; Bossert, Adam et al. (2016) Immunogenicity of a Prefusion HIV-1 Envelope Trimer in Complex with a Quaternary-Structure-Specific Antibody. J Virol 90:2740-55
Stewart-Jones, Guillaume B E; Soto, Cinque; Lemmin, Thomas et al. (2016) Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell 165:813-26
Barbian, Hannah J; Decker, Julie M; Bibollet-Ruche, Frederic et al. (2015) Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas. MBio 6:
Kong, Leopold; Wilson, Ian A; Kwong, Peter D (2015) Crystal structure of a fully glycosylated HIV-1 gp120 core reveals a stabilizing role for the glycan at Asn262. Proteins 83:590-6

Showing the most recent 10 out of 38 publications