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Visualizing HIV-1 capsid and its interactions with antivirals and host factors

DOI: 10.3390/v13020246 DOI Help

Authors: Morganne Wilbourne (Magdalen College, University of Oxford) , Peijun Zhang (Diamond Light Source; University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Viruses , VOL 13

State: Published (Approved)
Published: February 2021

Open Access Open Access

Abstract: Understanding of the construction and function of the HIV capsid has advanced considerably in the last decade. This is due in large part to the development of more sophisticated structural techniques, particularly cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET). The capsid is known to be a pleomorphic fullerene cone comprised of capsid protein monomers arranged into 200–250 hexamers and 12 pentamers. The latter of these induce high curvature necessary to close the cone at both ends. CryoEM/cryoET, NMR, and X-ray crystallography have collectively described these interactions to atomic or near-atomic resolutions. Further, these techniques have helped to clarify the role the HIV capsid plays in several parts of the viral life cycle, from reverse transcription to nuclear entry and integration into the host chromosome. This includes visualizing the capsid bound to host factors. Multiple proteins have been shown to interact with the capsid. Cyclophilin A, nucleoporins, and CPSF6 promote viral infectivity, while MxB and Trim5α diminish the viral infectivity. Finally, structural insights into the intra- and intermolecular interactions that govern capsid function have enabled development of small molecules, peptides, and truncated proteins to disrupt or stabilize the capsid to inhibit HIV replication. The most promising of these, GS6207, is now in clinical trial.

Journal Keywords: HIV-1; capsid; host proteins; antivirals; small molecules; restriction factors; CryoEM; CryoET; X-ray crystallography; NMR

Diamond Keywords: Human Immunodeficiency Virus (HIV); Viruses

Subject Areas: Biology and Bio-materials


Technical Areas:

Added On: 15/02/2021 13:05

Documents:
viruses-13-00246-v2.pdf

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Drug Discovery Infectious Diseases Pathogens Structural biology

Technical Tags: