2024 Research Highlights

B-HIVE researchers presented new work at the West Coast Retroviral Meeting in Palm Springs, October 3-5, 2024.

Neuro-microglial immune underlying HIV and substance use comorbidity

Narae Ahn, Soumya S Mahapatra, Janet P Zayas, Chandravanu Dash, João Mamede, Sumit K. Chanda, Sunnie M Yoh

Survey of mature retrovirus capsid lattice structures

Savannah G Brancato, Kristina Ambrus, Clifton L Ricaña, Robert A Dick

Rational design and evaluation of lenacapavir analogs for improved inhibition of HIV-1 Gag assembly

Mia Faerch, Daniel Adu-Ampratwum, Chet Oja, Mamuka Kvaratskhelia, Stefan G Sarafianos, Robert A Dick, Bruce E Torbett

Decoding the spliced HIV-1 transcriptome in resting CD4+ T-cells and T-cell subsets

Christian M Gallardo, Nadejda Beliakova-Bethell, Bruce E Torbett

Primary cell culture models for the study of HIV/HBV co-infection 

Adriana C Norris, Christopher E Jones, Christian M Beusch, Georgios Dangas, Kenneth C Levenson, Luana Barbosa, Yichen Zhou, Chenhui Zhou, David E Gordon, Ype P de Jong, Stefan G Sarafianos, Eleftherios Michailidis

Quantitative proteomic mapping of the cellular microenvironment to identify proteins contributing to HIV-1 Gag assembly

Jade Wolff, Tai-Wei Li, Shentian Zhuang, Corinne Thomas, Tien Le, Mia Faerch, Catherina Scharager-Tapia, Sung Kyu Park, John R Yates III, George Tsaprailis, Bruce E Torbett

Synthesis of new GS-6207 subtypes for targeting HIV-1 capsid protein

An effective approach for synthesizing inhibitors for HIV-1 capsid is presented.

Akther T, McFadden WM, Zhang H, Kirby KA, Sarafianos SG, Wang Z. Design and Int J Mol Sci. 2024 Mar 27;25(7):3734. doi: 10.3390/ijms25073734.

PubMed PMID: 38612545

PubMedCentral PMCID: PMC11012105

Overcoming resolution attenuation during tilted cryo-EM data collection

Cooperative membrane binding of HIV-1 matrix proteins

Long simulations explore the changing interactions of matrix proteins as they interact with the viral membrane.

Banerjee P, Monje-Galvan V, Voth GA. J Phys Chem B. 2024 Mar 21;128(11):2595-2606. doi: 10.1021/acs.jpcb.3c06222. Epub 2024 Mar 13.

PubMed PMID: 38477117

PubMedCentral PMCID: PMC10962350

Molecular dynamics simulations of HIV-1 matrix-membrane interactions at different stages of viral maturation

Simulations reveal the atomic details of multiple lipid binding sites in HIV-1 matrix protein.

Banerjee P, Qu K, Briggs JAG, Voth GA. Biophys J. 2024 Feb 6;123(3):389-406. doi: 10.1016/j.bpj.2024.01.006. Epub 2024 Jan 9.

PubMed PMID: 38196190

PubMedCentral PMCID: PMC10870173

Conformational transitions of the HIV-1 Gag polyprotein upon multimerization and gRNA binding

Computational modeling explores changes in conformation as HIV-1 Gag protein assembles.

Banerjee P, Voth GA. Biophys J. 2024 Jan 2;123(1):42-56. doi: 10.1016/j.bpj.2023.11.017. Epub 2023 Nov 18.

PubMed PMID: 37978800

Kinetic coevolutionary models predict the temporal emergence of HIV-1 resistance mutations under drug selection pressure

A tag-free platform for synthesis and screening of cyclic peptide libraries

HIV-1 uncoating requires long double-stranded reverse transcription products

Long double-stranded DNA triggers efficient uncoating of the HIV-1 genome from capsid cores.

Burdick, R. C., Morse, M., Rouzina, I., Williams, M. C., Hu, W. S., & Pathak, V. K. (2024). Science advances10(17), eadn7033. https://doi.org/10.1126/sciadv.adn7033

PubMed PMID: 38657061

PubMedCentral PMCID: PMC11042746

HIV-1 capsid uncoating Is a multistep process that proceeds through defect formation followed by disassembly of the capsid lattice

Fluorescently labeled virus capsids provide evidence that uncoating occurs inside the nucleus.

Gifford LB, Melikyan GB. ACS Nano. 2024 Jan 30;18(4):2928-2947. doi: 10.1021/acsnano.3c07678. Epub 2024 Jan 19.

PubMed PMID: 38241476

PubMedCentral PMCID: PMC10832047

Structural basis of branching during RNA splicing

Cryoelectron microscopy reveals an early step in splicing of introns from messenger RNA.

Haack DB, Rudolfs B, Zhang C, Lyumkis D, Toor N. Nat Struct Mol Biol. 2024 Jan;31(1):179-189. doi: 10.1038/s41594-023-01150-0. Epub 2023 Dec 6.

PubMed PMID: 38057551

PubMedCentral PMCID: PMC10968580

HIV-1 capsid shape, orientation, and entropic elasticity regulate translocation into the nuclear pore complex

Coarse grain modeling is used to explore how capsids with different shapes are transported through nuclear pores.

Hudait A, Voth GA. Proc Natl Acad Sci U S A. 2024 Jan 23;121(4):e2313737121. doi: 10.1073/pnas.2313737121. Epub 2024 Jan 19.

PubMed PMID: 38241438

PubMedCentral PMCID: PMC10823262

Synergy of machine learning and density functional theory calculations for predicting experimental Lewis base affinity and Lewis polybase binding atoms

Advanced machine learning methods are developed to predict the affinity of inhibitors to protein targets.

Huynh H, Le K, Vu L, Nguyen T, Holcomb M, Forli S, Phan H. J Comput Chem. 2024 Mar 18. doi: 10.1002/jcc.27329.

PubMed PMID: 38500409

Identification of clickable HIV-1 capsid-targeting probes for viral replication inhibition

Elucidating the molecular determinants of the binding modes of a third-generation HIV-1 integrase strand transfer inhibitor: The importance of side chain and solvent reorganization

A novel molecular dynamics method reveals the molecular details of how HIV-1 integrase recognizes strand transfer inhibitors.

Sun Q, Biswas A, Lyumkis D, Levy R, Deng N. Viruses. 2024 Jan 2;16(1):76. doi: 10.3390/v16010076.

PubMed PMID: 38257776

Human T-cell leukemia virus type 1 uses a specific tRNAPro isodecoder to prime reverse transcription

B-HIVE researchers explore the priming of reverse transcription in the only known oncogenic human retrovirus.

Syu, Y. C., Hatterschide, J., Budding, C. R., Tang, Y., & Musier-Forsyth, K. (2024). RNA (New York, N.Y.)30(8), 967–976. https://doi.org/10.1261/rna.080006.124

PubMed PMID: 38684316

PubMedCentral PMCID: PMC11251516

Missing wedge completion via unsupervised learning with coordinate networks

Bipartite viral RNA genome heterodimerization influences genome packaging and virion thermostability

A next generation sequencing approach explores the interaction of RNA in viruses that encode their genome in multiple strands.

Zhou Y, Routh AL. J Virol. 2024 Mar 19;98(3):e0182023. doi: 10.1128/jvi.01820-23. Epub 2024 Feb 8.

PubMed PMID: 38329331

PubMedCentral PMCID: PMC10949487