The human antiviral protein MxB is a restriction factor that fights HIV infection. Previous experiments have demonstrated that MxB targets the HIV capsid, a protein shell that protects the viral genome. To make the conical-shaped capsid, HIV CA proteins are organized into a lattice composed of hexamer and pentamer building blocks, providing many interfaces for host proteins to recognize. Through extensive biochemical and biophysical studies and molecular dynamics simulations, we show that MxB is targeting the HIV capsid by recognizing the region created at the intersection of three CA hexamers. We are further able to map this interaction to a few CA residues, located in a negatively charged well at the interface between the three CA hexamers. This work provides detailed residue-level mapping of the targeted capsid interface and how MxB interacts. This information could inspire the development of capsid-targeting therapies for HIV.
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http://dx.doi.org/10.1016/j.str.2019.04.015 | DOI Listing |
Cell Rep
January 2025
Gladstone Institutes, San Francisco, CA, USA; Department of Urology, UCSF, San Francisco, CA, USA. Electronic address:
We developed viral sensor and restriction factor-cytometry by time of flight (VISOR-CyTOF), which profiles 19 viral sensors and restriction factors (VISORs) simultaneously in single cells, and applied it to 41 postmortem tissues from people with HIV. Mucosal myeloid cells are well equipped with SAMHD1 and sensors of viral capsid and DNA while CD4 T cells are not. In lymph node CD4 Tfh, VISOR expression patterns reflect those favoring integration but blocking HIV gene expression, thus favoring viral latency.
View Article and Find Full Text PDFMolecules
December 2024
School of Electrical Engineering, Shandong University, Jinan 250061, China.
In recent years, plasma medicine has developed rapidly as a new interdisciplinary discipline. However, the key mechanisms of interactions between cold atmospheric plasma (CAP) and biological tissue are still in the exploration stage. In this study, by introducing the reactive molecular dynamics (MD) simulation, the capsid protein (CA) molecule of HIV was selected as the model to investigate the reaction process upon impact by reactive oxygen species (ROS) from CAP and protein molecules at the atomic level.
View Article and Find Full Text PDFHIV-1 assembly is initiated by the binding of Gag polyproteins to the inner leaflet of the plasma membrane, mediated by the myristylated matrix (MA) domain of Gag. Subsequent to membrane binding, Gag oligomerizes and buds as an immature, non-infectious virus particle, which, upon cleavage of the Gag precursor by the viral protease, transforms into a mature, infectious virion. During maturation, the MA lattice underlying the viral membrane undergoes a structural rearrangement and the newly released capsid (CA) protein forms a mature capsid that encloses the viral genome.
View Article and Find Full Text PDFRSC Adv
January 2025
Xinjiang Laboratory of Phase Transitions and Microstructures in Condensed Matter Physics, College of Physical Science and Technology, Yili Normal University Yining 835000 China
Molecular dynamics (MD) with the ReaxFF force field is used to study the structural damage to HIV capsid protein and gp120 protein mediated by reactive oxygen species (ROS). Our results show that with an increase in ROS concentration, the structures of the HIV capsid protein and gp120 protein are more severely damaged, including dehydrogenation, increase in oxygen-containing groups, helix shortening or destruction, and peptide bond breaking. In particular, we noticed that extraction of H atoms from N atoms by ROS was significantly higher than that from C atoms.
View Article and Find Full Text PDFNat Med
January 2025
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
The clinical management of people with multidrug-resistant (MDR) human immunodeficiency virus (HIV) remains challenging despite continued development of antiretroviral agents. A 58-year-old male individual with MDR HIV and Kaposi sarcoma (KS) was treated with a new antiretroviral regimen consisting of anti-CD4 domain 1 antibody UB-421 and capsid inhibitor lenacapavir. The individual experienced delayed but sustained suppression of plasma viremia and a substantial increase in the CD4 T cell count.
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