scholarly journals A supramolecular assembly mediates lentiviral DNA integration

Science ◽  
2017 ◽  
Vol 355 (6320) ◽  
pp. 93-95 ◽  
Author(s):  
Allison Ballandras-Colas ◽  
Daniel P. Maskell ◽  
Erik Serrao ◽  
Julia Locke ◽  
Paolo Swuec ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Supramolecular Assembly ◽  
Structural Data ◽  
Higher Order ◽  
Viral Dna ◽  
Dna Integration ◽  
Cryo Electron Microscopy ◽  
Nucleoprotein Complex ◽  
Retroviral Integrase ◽  
Hiv 1

Retroviral integrase (IN) functions within the intasome nucleoprotein complex to catalyze insertion of viral DNA into cellular chromatin. Using cryo–electron microscopy, we now visualize the functional maedi-visna lentivirus intasome at 4.9 angstrom resolution. The intasome comprises a homo-hexadecamer of IN with a tetramer-of-tetramers architecture featuring eight structurally distinct types of IN protomers supporting two catalytically competent subunits. The conserved intasomal core, previously observed in simpler retroviral systems, is formed between two IN tetramers, with a pair of C-terminal domains from flanking tetramers completing the synaptic interface. Our results explain how HIV-1 IN, which self-associates into higher-order multimers, can form a functional intasome, reconcile the bulk of early HIV-1 IN biochemical and structural data, and provide a lentiviral platform for design of HIV-1 IN inhibitors.

scholarly journals Modeling the Late Steps in HIV-1 Retroviral Integrase-catalyzed DNA Integration

2000 ◽  
Vol 275 (50) ◽  
pp. 39287-39295 ◽  
Author(s):  
Elena Brin ◽  
Jizu Yi ◽  
Anna Marie Skalka ◽  
Jonathan Leis
Keyword(s):  
Dna Integration ◽  
Retroviral Integrase ◽  
Hiv 1

scholarly journals Prefusion structure of trimeric HIV-1 envelope glycoprotein determined by cryo-electron microscopy

2013 ◽  
Vol 20 (12) ◽  
pp. 1352-1357 ◽  
Author(s):  
Alberto Bartesaghi ◽  
Alan Merk ◽  
Mario J Borgnia ◽  
Jacqueline L S Milne ◽  
Sriram Subramaniam
Keyword(s):  
Electron Microscopy ◽  
Envelope Glycoprotein ◽  
Cryo Electron Microscopy ◽  
Hiv 1

scholarly journals Networks of HIV-1 envelope glycans maintain antibody epitopes in the face of glycan additions and deletions

2020 ◽  
Author(s):  
Gemma E. Seabright ◽  
Christopher A. Cottrell ◽  
Marit J. van Gils ◽  
Alessio D’addabbo ◽  
David J. Harvey ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Neutralizing Antibodies ◽  
Broadly Neutralizing Antibodies ◽  
Site Specific ◽  
Glycan Analysis ◽  
Cryo Electron Microscopy ◽  
Immunogen Design ◽  
The Face ◽  
Antibody Epitopes ◽  
Hiv 1

SUMMARYNumerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans. Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal the hierarchy of importance of glycans in the formation of the 2G12 bnAb epitope, and show that the epitope is only subtly impacted by variations in the glycan network. In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans. Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.

scholarly journals Cryo-electron microscopy reveals ordered domains in the immature HIV-1 particle

1997 ◽  
Vol 7 (10) ◽  
pp. 729-738 ◽  
Author(s):  
Stephen D. Fuller ◽  
Thomas Wilk ◽  
Brent E. Gowen ◽  
Hans-Georg Kräusslich ◽  
Volker M. Vogt
Keyword(s):  
Electron Microscopy ◽  
Cryo Electron Microscopy ◽  
Hiv 1

scholarly journals APOBEC3F and APOBEC3G Inhibit HIV-1 DNA Integration by Different Mechanisms

2010 ◽  
Vol 84 (10) ◽  
pp. 5250-5259 ◽  
Author(s):  
Jean L. Mbisa ◽  
Wei Bu ◽  
Vinay K. Pathak
Keyword(s):  
Catalytic Domain ◽  
Restriction Factors ◽  
Viral Dna ◽  
Dna Integration ◽  
Host Restriction ◽  
Antiviral Activities ◽  
Viral Cdna ◽  
Viral Dna Integration ◽  
Cytidine Deamination ◽  
Hiv 1

ABSTRACT APOBEC3F (A3F) and APBOBEC3G (A3G) both are host restriction factors that can potently inhibit human immunodeficiency virus type 1 (HIV-1) replication. Their antiviral activities are at least partially mediated by cytidine deamination, which causes lethal mutations of the viral genome. We recently showed that A3G blocks viral plus-strand DNA transfer and inhibits provirus establishment in the host genome (J. L. Mbisa, R. Barr, J. A. Thomas, N. Vandegraaff, I. J. Dorweiler, E. S. Svarovskaia, W. L. Brown, L. M. Mansky, R. J. Gorelick, R. S. Harris, A. Engelman, and V. K. Pathak, J. Virol. 81:7099-7110, 2007). Here, we investigated whether A3F similarly interferes with HIV-1 provirus formation. We observed that both A3F and A3G inhibit viral DNA synthesis and integration, but A3F is more potent than A3G in preventing viral DNA integration. We further investigated the mechanisms by which A3F and A3G block viral DNA integration by analyzing their effects on viral cDNA processing using Southern blot analysis. A3G generates a 6-bp extension at the viral U5 end of the 3′ long terminal repeat (3′-LTR), which is a poor substrate for integration; in contrast, A3F inhibits viral DNA integration by reducing the 3′ processing of viral DNA at both the U5 and U3 ends. Furthermore, we demonstrated that a functional C-terminal catalytic domain is more critical for A3G than A3F function in blocking HIV-1 provirus formation. Finally, we showed that A3F has a greater binding affinity for a viral 3′-LTR double-stranded DNA (dsDNA) oligonucleotide template than A3G. Taking these results together, we demonstrated that mechanisms utilized by A3F to prevent HIV-1 viral DNA integration were different from those of A3G, and that their target specificities and/or their affinities for dsDNA may contribute to their distinct mechanisms.

scholarly journals HIV-1 Mutants that Escape the Cytotoxic T-Lymphocytes are Defective in Viral DNA Integration

2021 ◽  
Author(s):  
Muthukumar Balasubramaniam ◽  
Santosh Thapa ◽  
Benem-Orom Davids ◽  
Alex Bryer ◽  
Chaoyi Xu ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Human Leukocyte ◽  
Virus Infectivity ◽  
Viral Dna ◽  
Ctl Response ◽  
Dna Integration ◽  
Viral Dna Integration ◽  
Hiv 1 ◽  
Selection Of

ABSTRACTHIV-1 replication is durably controlled in certain untreated HIV-1-infected individuals expressing particular human leukocyte antigens (HLA). These HLAs tag infected cells for elimination by presenting specific viral epitopes to CD8+ cytotoxic T-lymphocytes (CTL). In individuals expressing HLA-B27, CTLs primarily target the capsid protein (CA)-derived KK10 epitope. Selection of CA mutation R264K helps HIV-1 escape the CTL response but severely diminishes virus infectivity. Here we report that the R264K mutation-associated infectivity defect arises primarily from impaired viral DNA integration. Strikingly, selection of the compensatory CA mutation S173A or depletion of host cyclophilin A largely rescues the R264K-associated integration and infectivity defects. Collectively, our study reveals novel mechanistic insights into the fitness defect incurred by an HIV-1 variant escaping a CA-directed CTL response.

Visualization of co-axially coiled dsDNA in bacteriophage T7 capsids by cryo-electron microscopy

1996 ◽  
Vol 54 ◽  
pp. 68-69
Author(s):  
Naiqian Cheng ◽  
Mario E. Cerritelli ◽  
Alan H. Rosenberg ◽  
Frank P. Booy ◽  
Alasdair C. Steven
Keyword(s):  
Electron Microscopy ◽  
Life Cycle ◽  
Bacteriophage T7 ◽  
Efficient Utilization ◽  
Viral Dna ◽  
Viral Capsids ◽  
Double Stranded Dna ◽  
Cryo Electron Microscopy ◽  
Invaluable Tool ◽  
Repulsive Forces

The packaging of viral DNA into a pre-formed procapsid structure and its subsequent release from the mature virion during infection, constitutes one of the basic phenomena of the viral life-cycle which still remains to be understood. The DNA must package at a high density into the head to allow efficient utilization of the space available, overcome the mutual electrostatic repulsive forces between the strands, and be readily available for release upon infection. Cryo-electron microscopy has proven to be an invaluable tool for visualizing the internal organization of the packaged DNA inside viral capsids. We report on the effectiveness of this technique in examining the packaging of the ∼40,000 bp double-stranded DNA genome inside the capsids of bacteriophage T7.

scholarly journals Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics

Nature ◽  
2013 ◽  
Vol 497 (7451) ◽  
pp. 643-646 ◽  
Author(s):  
Gongpu Zhao ◽  
Juan R. Perilla ◽  
Ernest L. Yufenyuy ◽  
Xin Meng ◽  
Bo Chen ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Molecular Dynamics ◽  
Cryo Electron Microscopy ◽  
Hiv 1
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