HIV type 1 (HIV-1) envelope glycoproteins (Env) mediate virus entry and are the target of neutralizing antibodies. Binding of the metastable HIV-1 Env trimer to the CD4 receptor triggers structural rearrangements that mediate Env conformational transitions from a closed conformation to a more open state through an intermediate step. Recent studies have revealed new insights on the dynamics, regulation, and molecular mechanisms of Env transitions along the entry pathway. In this study, we provide an overview of the current knowledge on Env conformational dynamics and the relationship between Env conformational states and neutralization selectivity of the broadly neutralizing antibodies that develop in 10%-20% of infected individuals and may provide guidance for the development of an effective HIV-1 vaccine.
Bibliographical noteFunding Information:
The authors thank Dr. Ashley Haase for critical reading of the article. A.H. is the recipient of an amfAR Mathilde Krim Fellowship in Basic Biomedical Research (108501-53-RKNT) and was also supported by a phase II amfAR research grant (109285-58-RKVA) for independent investigators. This work was supported by internal funds of the Department of Medicine at the University of Minnesota. This work is dedicated to Dr. Mathilde Krim who laid the foundation for continuous support for young and promising researchers in the HIV-1 field during their transition to independent research positions in leading academic institutes.
© Copyright 2018, Mary Ann Liebert, Inc., publishers 2018.
- HIV-1 entry
- HIV-1 envelope glycoproteins
- broadly neutralizing antibodies
- conformational transitions