High-Definition Analysis of Host Protein Stability during Human Cytomegalovirus Infection Reveals Antiviral Factors and Viral Evasion Mechanisms DOI Creative Commons
Katie Nightingale, Kai‐Min Lin,

Benjamin J. Ravenhill

et al.

Cell Host & Microbe, Journal Year: 2018, Volume and Issue: 24(3), P. 447 - 460.e11

Published: Aug. 16, 2018

Human cytomegalovirus (HCMV) is an important pathogen with multiple immune evasion strategies, including virally facilitated degradation of host antiviral restriction factors. Here, we describe a multiplexed approach to discover proteins innate function on the basis active by proteasome or lysosome during early-phase HCMV infection. Using three orthogonal proteomic/transcriptomic screens quantify protein degradation, high confidence identified 35 enriched in A final screen employed comprehensive panel viral mutants predict genes that target >250 human proteins. This revealed helicase-like transcription factor (HLTF), DNA helicase repair, potently inhibits early gene expression but rapidly degraded The functionally unknown UL145 facilitates HLTF recruiting Cullin4 E3 ligase complex. Our and data will enable further identifications pathways targeted other viruses.

Language: Английский

Interferon-Stimulated Genes: A Complex Web of Host Defenses DOI Open Access
William M. Schneider, Meike Dittmann, Charles M. Rice

et al.

Annual Review of Immunology, Journal Year: 2014, Volume and Issue: 32(1), P. 513 - 545

Published: Feb. 20, 2014

Interferon-stimulated gene (ISG) products take on a number of diverse roles. Collectively, they are highly effective at resisting and controlling pathogens. In this review, we begin by introducing interferon (IFN) the JAK-STAT signaling pathway to highlight features that impact ISG production. Next, describe ways in which ISGs both enhance innate pathogen-sensing capabilities negatively regulate through pathway. Several directly inhibit virus infection described with an emphasis those early late stages life cycle. Finally, ongoing efforts identify characterize antiviral ISGs, provide forward-looking perspective landscape.

Language: Английский

Citations

2718
Pathways to zoonotic spillover DOI Open Access
Raina K. Plowright, Colin R. Parrish, Hamish McCallum

et al.

Nature Reviews Microbiology, Journal Year: 2017, Volume and Issue: 15(8), P. 502 - 510

Published: May 30, 2017

Language: Английский

Citations

1021
Cytosolic Sensing of Viruses DOI Creative Commons

Delphine Goubau,

Safia Deddouche,

Caetano Reis e Sousa

et al.

Immunity, Journal Year: 2013, Volume and Issue: 38(5), P. 855 - 869

Published: May 1, 2013

Language: Английский

Citations

778
IFITM-Family Proteins: The Cell's First Line of Antiviral Defense DOI Open Access
Charles C. Bailey, Guocai Zhong,

I‐Chueh Huang

et al.

Annual Review of Virology, Journal Year: 2014, Volume and Issue: 1(1), P. 261 - 283

Published: July 8, 2014

Animal cells use a wide variety of mechanisms to slow or prevent replication viruses. These are usually mediated by antiviral proteins whose expression and activities can be constitutive but frequently amplified interferon induction. Among these interferon-stimulated proteins, members the IFITM (interferon-induced transmembrane) family unique because they infection before virus traverse lipid bilayer cell. At least three human proteins-IFITM1, IFITM2, IFITM3-have activities. limit in cultured many viruses, including dengue virus, Ebola influenza A severe acute respiratory syndrome coronavirus, West Nile virus. Murine Ifitm3 controls vivo, polymorphisms IFITM3 correlate with severity both seasonal highly pathogenic avian Here we review discovery characterization describe spectrum their activities, discuss potential underlying effects.

Language: Английский

Citations

428
HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation DOI
Annachiara Rosa, Ajit Chande,

Serena Ziglio

et al.

Nature, Journal Year: 2015, Volume and Issue: 526(7572), P. 212 - 217

Published: Sept. 29, 2015

Language: Английский

Citations

418
Quantitative Temporal Viromics: An Approach to Investigate Host-Pathogen Interaction DOI Creative Commons
Michael P. Weekes, Peter Tomašec, Edward L. Huttlin

et al.

Cell, Journal Year: 2014, Volume and Issue: 157(6), P. 1460 - 1472

Published: June 1, 2014

A systematic quantitative analysis of temporal changes in host and viral proteins throughout the course a productive infection could provide dynamic insights into virus-host interaction. We developed proteomic technique called "quantitative viromics" (QTV), which employs multiplexed tandem-mass-tag-based mass spectrometry. Human cytomegalovirus (HCMV) is not only an important pathogen but paradigm immune evasion. QTV detailed how HCMV orchestrates expression >8,000 cellular proteins, including 1,200 cell-surface to manipulate signaling pathways counterintrinsic, innate, adaptive defenses. predicted natural killer T cell ligands, as well 29 present at surface, potential therapeutic targets. Temporal profiles >80% canonical genes 14 noncanonical open reading frames were defined. powerful method that can yield applicable any virus with robust vitro model.PaperClip/cms/asset/73b31c12-81e5-4c68-a7e8-ca7ba21cc6ce/mmc10.mp3Loading ...(mp3, 3.16 MB) Download audio

Language: Английский

Citations

417
Evolutionary insights into host–pathogen interactions from mammalian sequence data DOI Open Access
Manuela Sironi, Rachele Cagliani, Diego Forni

et al.

Nature Reviews Genetics, Journal Year: 2015, Volume and Issue: 16(4), P. 224 - 236

Published: March 18, 2015

Language: Английский

Citations

270
Constitutive immune mechanisms: mediators of host defence and immune regulation DOI Open Access
Søren R. Paludan, Thomas Pradeu, Seth L. Masters

et al.

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 21(3), P. 137 - 150

Published: Aug. 11, 2020

Language: Английский

Citations

259
IFITM Proteins Incorporated into HIV-1 Virions Impair Viral Fusion and Spread DOI Creative Commons
Alex A. Compton, Timothée Bruel, Françoise Porrot

et al.

Cell Host & Microbe, Journal Year: 2014, Volume and Issue: 16(6), P. 736 - 747

Published: Nov. 26, 2014

Language: Английский

Citations

203
Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import DOI Creative Commons
Veronika Götz,

Linda Magar,

Dominik Dornfeld

et al.

Scientific Reports, Journal Year: 2016, Volume and Issue: 6(1)

Published: March 18, 2016

Abstract To establish a new lineage in the human population, avian influenza A viruses (AIV) must overcome intracellular restriction factor MxA. Partial escape from MxA can be achieved when viral nucleoprotein (NP) acquires critical human-adaptive amino acid residues 100I/V, 283P, and 313Y. Here, we show that introduction of these three into NP an H5N1 virus renders it genetically unstable, resulting harboring additional single mutations, including G16D. These substitutions restored genetic stability yet again yielded with varying degrees attenuation mammalian cells. Additionally, most mutant lost capacity to restriction, exception G16D virus. We is linked by demonstrating promoting disturbed trafficking incoming ribonucleoprotein complexes (vRNPs), thereby impaired nuclear import, acquired mutations only partially compensate for this import block. conclude adaptation host, AIV not but also associated block vRNP import. This inherent difficulty may explain frequent failure become pandemic.

Language: Английский

Citations

196