2022 Research Highlights

Multivalent interactions essential for lentiviral integrase function

Limits to detecting epistasis in the fitness landscape of HIV

Interactions between mutations affect viral fitness, but may be difficult to observe experimentally.

Biswas A, Haldane A, Levy RM.  PLoS One. 2022 Jan 18;17(1):e0262314. doi: 10.1371/journal.pone.0262314.

PubMed PMID: 35041711

PubMedCentral PMCID: PMC8765623

Phosphomimetic S207D lysyl-tRNA synthetase binds HIV-1 5’UTR in an open conformation and increases RNA dynamics

Phosphorylated lysyl-tRNA synthetase may be important for delivering primer tRNAs to HIV-1 genomic RNA.

Cantara WA, Pathirage C, Hatterschide J, Olson ED, Musier-Forsyth K. Viruses. 2022 Jul 16;14(7):1556. doi: 10.3390/v14071556.

PubMed PMID: 35891536

PubMedCentral PMCID: PMC9315659

Drug interactions in lenacapavir-based long-acting antiviral combinations

Combinations of capsid inhibitors and reverse transcriptase inhibitors are explored for long-acting treatment of HIV-1.

Cilento ME, Ong YT, Tedbury PR, Sarafianos SG.  Viruses. 2022 May 31;14(6):1202. doi: 10.3390/v14061202.

PubMed PMID: 35746673

PubMedCentral PMCID: PMC9229705

Unique features of different classes of G-protein-coupled receptors revealed from sequence coevolutionary and structural analysis

Covariation analysis of GPCR sequences is used to reveal sites involved in activation and allosteric regulation.

Do HN, Haldane A, Levy RM, Miao Y.  Proteins. 2022 Feb;90(2):601-614. doi: 10.1002/prot.26256. Epub 2021 Oct 9.

PubMed PMID: 34599827

PubMedCentral PMCID: PMC8738117 (available on 2023-02-01)

Multimodal functionalities of HIV-1 integrase

B-HIVE Center researchers review HIV-1 integrase mutants that cause defects in maturation.

Engelman AN, Kvaratskhelia M. Viruses. 2022 Apr 28;14(5):926. doi: 10.3390/v14050926.

PubMed PMID: 35632668

PubMedCentral PMCID: PMC9144474

Selective ablation of 3′ RNA ends and processive RTs facilitate direct cDNA sequencing of full-length host cell and viral transcripts

A new sequencing method reveals alternative splicing of RNA within a host cell transcriptome.

Gallardo CM, Nguyen AT, Routh AL, Torbett BE.  Nucleic Acids Res. 2022 Jun 23:gkac516. doi: 10.1093/nar/gkac516. Epub ahead of print.

PubMed PMID: 35736235

HIV-1 nucleocapsid protein binds double-stranded DNA in multiple modes to regulate compaction and capsid uncoating

Optical tweezers, fluorescence imaging, and atomic force microscopy are used to explore the interaction of HIV-1 nucleocapsid and DNA.

Gien H, Morse M, McCauley MJ, Kitzrow JP, Musier-Forsyth K, Gorelick RJ, Rouzina I, Williams MC.  Viruses. 2022 Jan 25;14(2):235. doi: 10.3390/v14020235.

PubMed PMID: 35215829

PubMedCentral PMCID: PMC8879225

Cryo-EM structure of the HIV-1 Pol polyprotein provides insights into virion maturation

Quantitative mining of compositional heterogeneity in cryo-EM datasets of ribosome assembly intermediates

A workflow is presented that quantitatively mines cryo-EM data to isolate sets of structures with maximal diversity.

Rabuck-Gibbons JN, Lyumkis D, Williamson JR.  Structure. 2022 Apr 7;30(4):498-509.e4. doi: 10.1016/j.str.2021.12.005. Epub 2022 Jan 5.

PubMed PMID: 34990602

Structural basis of HIV inhibition by L-nucleosides: Opportunities for drug development and repurposing

The structure, function and future uses of L-nucleoside inhibitors is reviewed.

Ruiz FX, Hoang A, Dilmore CR, DeStefano JJ, Arnold E.  Drug Discov Today. 2022 Jul;27(7):1832-1846. doi: 10.1016/j.drudis.2022.02.016. Epub 2022 Feb 23.

PubMed PMID: 35218925

PubMedCentral PMCID: PMC9232924 (available on 2023-07-01)

TRIM5α restriction of HIV-1-N74D viruses in lymphocytes is caused by a loss of cyclophilin A protection

A mutation in HIV-1 capsid blocks binding to cyclophilin A, leading to reduced infectivity of the virus.

Selyutina A, Simons LM, Kirby KA, Bulnes-Ramos A, Hu P, Sarafianos SG, Hultquist JF, Diaz-Griffero F.  Viruses. 2022 Feb 10;14(2):363. doi: 10.3390/v14020363.

PubMed PMID: 35215956

PubMedCentral PMCID: PMC8879423

Structure-based virtual screening workflow to identify antivirals targeting HIV-1 capsid

A combination of computational docking and advanced free energy estimation is used to discover new HIV-1 inhibitors.

Sun Q, Biswas A, Vijayan RSK, Craveur P, Forli S, Olson AJ, Castaner AE, Kirby KA, Sarafianos SG, Deng N, Levy R.  J Comput Aided Mol Des. 2022 Mar;36(3):193-203. doi: 10.1007/s10822-022-00446-5. Epub 2022 Mar 9.

PubMed PMID: 35262811

PubMedCentral PMCID: PMC8904208

An optimized measles virus glycoprotein-pseudotyped lentiviral vector production system to promote efficient transduction of human primary B cells

A efficient protocol is presented to package complex transgene-containing lentiviral vectors.

Vamva E, Ozog S, Verhoeyen E, James RG, Rawlings DJ, Torbett BE.  STAR Protoc. 2022 Mar 8;3(1):101228. doi: 10.1016/j.xpro.2022.101228.

PubMed PMID: 35284833

PubMedCentral PMCID: PMC8914380

Covariation of viral recombination with single nucleotide variants during virus evolution revealed by CoVaMa

Analysis of Flock House virus sequences reveals that recombination and point mutations of the genome are intimately linked.

Wang S, Sotcheff SL, Gallardo CM, Jaworski E, Torbett BE, Routh AL. Nucleic Acids Res. 2022 Apr 22;50(7):e41. doi: 10.1093/nar/gkab1259.

PubMed PMID: 35018461

PubMedCentral PMCID: PMC9023271

Next-generation sequencing: A new avenue to understand viral RNA-protein interactions

Recent advances in next-generation sequencing technologies have allowed the characterization of viral RNA-protein interactions.

Zhou Y, Sotcheff SL, Routh AL.  J Biol Chem. 2022 May;298(5):101924. doi: 10.1016/j.jbc.2022.101924. Epub 2022 Apr 9.

PubMed PMID: 35413291

PubMedCentral PMCID: PMC8994257