Integrative modeling of the HIV-1 ribonucleoprotein complex

A coarse-grain computational method integrates biophysical and structural data to generate models of HIV-1 genomic RNA, nucleocapsid and integrase condensed into a mature ribonucleoprotein complex. Several hypotheses for the initial structure of the genomic RNA and oligomeric state of integrase are tested. In these models, integrase interaction captures features of the relative distribution of gRNA in the immature virion and increases the size of the RNP globule, and exclusion of nucleocapsid from regions with RNA secondary structure drives an asymmetric placement of the dimerized 5’UTR at the surface of the RNP globule.

[1]  G. Voth,et al.  Early stages of the HIV-1 capsid protein lattice formation. , 2012, Biophysical journal.

[2]  B. Gowen,et al.  Organization of Immature Human Immunodeficiency Virus Type 1 , 2001, Journal of Virology.

[3]  B. Berkhout,et al.  The leader of the HIV-1 RNA genome forms a compactly folded tertiary structure. , 2000, RNA.

[4]  K. Moelling,et al.  Conformational and nucleic acid binding studies on the synthetic nucleocapsid protein of HIV-1. , 1993, Journal of molecular biology.

[5]  Jean Sturm,et al.  Persistence Length of Single-Stranded DNA , 1997 .

[6]  R. Ghirlando,et al.  Cryo-EM structures and atomic model of the HIV-1 strand transfer complex intasome , 2017, Science.

[7]  I. Amit,et al.  Comprehensive mapping of long range interactions reveals folding principles of the human genome , 2011 .

[8]  Gregory A Voth,et al.  Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly , 2016, Nature Communications.

[9]  P. Bieniasz,et al.  HIV-1 Integrase Binds the Viral RNA Genome and Is Essential during Virion Morphogenesis , 2016, Cell.

[10]  H. Kräusslich,et al.  Biochemical and Structural Analysis of Isolated Mature Cores of Human Immunodeficiency Virus Type 1 , 2000, Journal of Virology.

[11]  J. Darlix,et al.  Properties and functions of the nucleocapsid protein in virus assembly , 2010, RNA biology.

[12]  S. Kamitori,et al.  Piecing together the structure of retroviral integrase , an important target in AIDS therapy , 2009 .

[13]  J. Briggs,et al.  Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution , 2014, Nature.

[14]  Kenneth A. Taylor,et al.  Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Gorodkin,et al.  Full-length RNA structure prediction of the HIV-1 genome reveals a conserved core domain , 2015, Nucleic acids research.

[16]  G. Jensen,et al.  Electron Cryotomography Studies of Maturing HIV-1 Particles Reveal the Assembly Pathway of the Viral Core , 2014, Journal of Virology.

[17]  Steve Plimpton,et al.  Fast parallel algorithms for short-range molecular dynamics , 1993 .

[18]  O. Kratky,et al.  Röntgenuntersuchung gelöster Fadenmoleküle , 1949 .

[19]  H. Kalbitzer,et al.  Human immunodeficiency virus type 1 Nef protein is incorporated into virus particles and specifically cleaved by the viral proteinase. , 1996, Virology.

[20]  Christopher L. Fillmore,et al.  Electron cryotomography of immature HIV‐1 virions reveals the structure of the CA and SP1 Gag shells , 2007, The EMBO journal.

[21]  J. Briggs,et al.  Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography , 2010, PLoS pathogens.

[22]  D. Goodsell Illustrations of the HIV life cycle. , 2015, Current topics in microbiology and immunology.

[23]  Ludovic Autin,et al.  Lattice Models of Bacterial Nucleoids. , 2018, The journal of physical chemistry. B.

[24]  Gregory A Voth,et al.  Multiscale computer simulation of the immature HIV-1 virion. , 2010, Biophysical journal.

[25]  Morgan C. Giddings,et al.  High-Throughput SHAPE Analysis Reveals Structures in HIV-1 Genomic RNA Strongly Conserved across Distinct Biological States , 2008, PLoS biology.

[26]  M. Jaskólski,et al.  Piecing together the structure of retroviral integrase, an important target in AIDS therapy , 2009, The FEBS journal.

[27]  Marc C. Johnson,et al.  The stoichiometry of Gag protein in HIV-1 , 2004, Nature Structural &Molecular Biology.

[28]  M. Yeager,et al.  Assembly and architecture of HIV. , 2012, Advances in experimental medicine and biology.

[29]  Stefano Forli,et al.  Art and Science of the Cellular Mesoscale. , 2020, Trends in biochemical sciences.

[30]  A. Engelman,et al.  Distribution and Redistribution of HIV-1 Nucleocapsid Protein in Immature, Mature, and Integrase-Inhibited Virions: a Role for Integrase in Maturation , 2015, Journal of Virology.