2018 Research Highlights

Capsid-CPSF6 interaction licenses nuclear HIV-1 trafficking to sites of viral DNA integration

Comparing alchemical and physical pathway methods for computing the absolute binding free energy of charged ligands

Foundational methods for predicting the binding strength of ligands to proteins are explored.

Deng N , Cui D , Zhang BW , Xia J , Cruz J , Levy R . Phys Chem Chem Phys. 2018 Jun 27;20(25):17081-17092.

PubMed PMID: 29896599

PubMedCentral PMCID: PMC6061996

Genetic and mechanistic basis for APOBEC3H alternative splicing, retrovirus restriction, and counteraction by HIV-1 protease

Analysis of variants of APOBEC3H reveal that HIV-1 protease plays a role in countering our cell’s defenses.

Ebrahimi D, Richards CM, Carpenter MA, Wang J, Ikeda T, Becker JT, Cheng AZ, McCann JL, Shaban NM, Salamango DJ, Starrett GJ, Lingappa JR, Yong J, Brown WL, Harris RS. Nat Commun. 9:4137 (2018).

PubMed PMID: 30297863

PubMedCentral PMCID: PMC6175962

Quantitative and orthogonal formation and reactivity of SuFEx platforms

New methods are presented for performing SuFEx reactions tethered to surfaces.

Gahtory D, Sen R, Pujari S, Li S, Zheng Q, Moses JE, Sharpless KB, Zuilhof H. Chemistry 24, 10550-10556 (2018).

PubMed PMID: 29949211

PubMedCentral PMCID: PMC6099289

SuFEx chemistry of thionyltetrafluoride (SOF(4)) with organolithium nucleophiles: Synthesis of sulfonimidoyl fluorides, sulfoximines, sulfonimidamides, and sulfonimidates

Thionyl tetrafluoride is used to create novel molecules through SuFEx click chemistry.

Gao B, Li S, Wu P, Moses JE, Sharpless KB. Angew. Chem. Int. Ed. Engl. 57,1939-1943 (2018).

PubMed PMID: 29314580

PubMedCentral PMCID: PMC6005182

CellPAINT: Interactive Illustration of Dynamic Mesoscale Cellular Environments

New software allows researchers and educators to create illustrations of HIV and host cells.

Gardner A, Autin L, Barbaro B, Olson AJ, Goodsell DS. IEEE Comput Graph Appl. 38, 51-66 (2018).

PubMed PMID: 30668455

PubMedCentral PMCID: PMC6456043

Coevolutionary landscape of kinase family proteins: Sequence probabilities and functional motifs

A coevolutionary model of sequence variations is used to identify functional regions in a protein family.

Haldane A, Flynn WF, He P, Levy RM. Biophys. J. 114, 21-31 (2018).

PubMed PMID: 29320688

PubMedCentral PMCID: PMC5773752

Effect of tRNA on the maturation of HIV-1 reverse transcriptase

Binding of transfer RNA is shown to induce asymmetry in reverse transcripase, enhancing its maturation.

Ilina TV, Slack RL, Elder JH, Sarafianos SG, Parniak MA, Ishima R. J. Mol. Biol. 430, 1891-1900 (2018).

PubMed PMID: 29751015

PubMedCentral PMCID: PMC5988984

Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na+/K+ transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses

Proteomics, genetics, and pharmacological validation identify an ion pump as a pro-viral factor in mammalian arenaviruses.

Iwasaki M, Minder P, Caì Y, Kuhn JH, Yates JR 3rd, Torbett BE, de la Torre JC. PLoS Pathog. 2018 Feb 20;14(2):e1006892.

PubMed PMID: 29462184

PubMedCentral PMCID: PMC5834214

Mutation signatures including APOBEC in cancer cell lines

The APOBEC mutation signature is enriched in some forms of cancer.

Jarvis MC, Ebrahimi D, Temiz NA, Harris RS. JNCI Cancer Spectr. 2018 Jan;2(1):pky002.

PubMed PMID: 29888758

PubMedCentral PMCID: PMC5993214

4′-Ethynyl-2-fluoro-2′-deoxyadenosine, MK-8591: a novel HIV-1 reverse transcriptase translocation inhibitor

The structure and function of the potent RT inhibitor EFdA is reviewed.

Markowitz M, Sarafianos SG. Curr Opin HIV AIDS 13, 294-299 (2018).

PubMed PMID: 29697468

PubMedCentral PMCID: PMC6449048

Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation

A proline-rich loop in the capsid domain plays an essential role in formation of HIV virions.

Novikova M, Adams LJ, Fontana J, Gres AT, Balasubramaniam M, Winkler DC, Kudchodkar SB, Soheilian F, Sarafianos SG, Steven AC, Freed EO. MBio 9, e01567-18 (2018).

PubMed PMID: 30327442

PubMedCentral PMCID: PMC6191540

Perspectives on structural molecular biology visualization: From past to present

A review of technical advances in visualization that support and drive research in structural molecular biology.

Olson AJ. J. Mol. Biol. 430, 3997-4012 (2018).

PubMed PMID: 30009769

PubMedCentral PMCID: PMC6186497

CD46 null packaging cell line improves measles lentiviral vector production and gene delivery to hematopoietic stem and progenitor cells

New methods to improve gene delivery to difficult-to-transduce cell types are explored

Ozog S, Chen CX, Simpson E, Garijo O, Timberlake ND, Minder P, Verhoeyen E, Torbett BE. Mol Ther Methods Clin Dev. 2018 Nov 24;13:27-39.

PubMed PMID: 30603655

PubMedCentral PMCID: PMC6310745

mTOR inhibitors lower an intrinsic barrier to virus infection mediated by IFITM3

The molecular basis of action of rapamycin and its role in virus entry is explored

Shi G, Ozog S, Torbett BE, Compton AA. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10069-E10078.

PubMed PMID: 30301809

PubMedCentral PMCID: PMC6205447

Visualization of HIV-1 RNA Transcription from Integrated HIV-1 DNA in Reactivated Latently Infected Cells

Flourescence microscopy is used to watch the reactivation of latent HIV-1.

Ukah OB, Puray-Chavez M, Tedbury PR, Herschhorn A, Sodroski JG, Sarafianos SG. Viruses 10, E534 (2018).

PubMed PMID: 30274333

PubMedCentral PMCID: PMC6212899

Human T-cell leukemia virus type 1 Gag domains have distinct RNA-binding specificities with implications for RNA packaging and dimerization

HIVE researchers discover that HTLV-1 matrix protein is involved in packaging of genomic RNA into virions.

Wu W, Hatterschide J, Syu YC, Cantara WA, Blower RJ, Hanson HM, Mansky LM, Musier-Forsyth K. J Biol Chem. 293,16261-16276 (2018).

PubMed PMID: 30217825

PubMedCentral PMCID: PMC6200928

Improving Prediction Accuracy of Binding Free Energies and Poses of HIV Integrase Complexes Using the Binding Energy Distribution Analysis Method with Flattening Potentials

HIVE Center researchers develop new methods for accurate prediction of binding free energies.

Xia J, Flynn W, Levy RM. J Chem Inf Model. 58, 1356-1371 (2018).

PubMed PMID: 29927237

PubMedCentral PMCID: PMC6287956

Structural Basis for the RNA-Guided Ribonuclease Activity of CRISPR-Cas13d

CryoEM reveals the atomic details of a CRISPR-Cas endonuclease.

Zhang C, Konermann S, Brideau NJ, Lotfy P, Wu X, Novick SJ, Strutzenberg T, Griffin PR, Hsu PD, Lyumkis D. Cell 175, 212-223.e17 (2018).

PubMed PMID: 30241607

PubMedCentral PMCID: PMC6179368

HIV-1 integrase-targeted short peptides derived from a viral protein R sequence

Small peptides from accessory protein Vpr provide a path to a new class of integrase inhibitors.

Zhao XZ, Métifiot M, Kiselev E, Kessl JJ, Maddali K, Marchand C, Kvaratskhelia M, Pommier Y, Burke TR Jr. Molecules. 2018 Jul 26;23(8):1858.

PubMed PMID: 30049955

PubMedCentral PMCID: PMC6222646

HDX-MS reveals dysregulated checkpoints that compromise discrimination against self RNA during RIG-I mediated autoimmunity

HDX-MS is used to explore the flexibility and function of a protein involved in immune surveillance of viral RNAs.

Zheng J, Wang C, Chang MR, Devarkar SC, Schweibenz B, Crynen GC, Garcia-Ordonez RD, Pascal BD, Novick SJ, Patel SS, Marcotrigiano J, Griffin PR. Nat Commun. 9, 5366 (2018).

PubMed PMID: 30560918

PubMedCentral PMCID: PMC6299088