Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Seminars in Immunopathology
Published in: Seminars in Immunopathology 6/2014

01-11-2014 | Review

Manipulation of host pathways by human cytomegalovirus: insights from genome-wide studies

Authors: Yifat Cohen, Noam Stern-Ginossar

Published in: Seminars in Immunopathology | Issue 6/2014

Login to get access

Abstract

The herpesvirus human cytomegalovirus (HCMV) infects the majority of the world’s population, leading to severe diseases in millions of newborns and immunocompromised adults annually. During infection, HCMV extensively manipulates cellular gene expression to maintain conditions favorable for efficient viral propagation. Identifying the pathways that the virus relies on or subverts is of great interest as they have the potential to provide new therapeutic targets and to reveal novel principles in cell biology. Over the past years, high-throughput analyses have profoundly broadened our understanding of the processes that occur during HCMV infection. In this review, we will discuss these new findings and how they impact our understanding of the biology of HCMV.
Literature
1.
Sinzger C, Digel M, Jahn G (2008) Cytomegalovirus cell tropism. Curr Top Microbiol Immunol 325:63–83PubMed
2.
Davison AJ, Dolan A, Akter P, Addison C, Dargan DJ, Alcendor DJ, McGeoch DJ, Hayward GS (2003) The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome. J Gen Virol 84:17–28PubMedCrossRef
3.
Murphy E, Yu D, Grimwood J, Schmutz J, Dickson M, Jarvis MA, Hahn G, Nelson JA, Myers RM, Shenk TE (2003) Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc Natl Acad Sci U S A 100:14976–14981PubMedCrossRefPubMedCentral
4.
Stern-Ginossar N, Weisburd B, Michalski A, Le VT, Hein MY, Huang SX, Ma M, Shen B, Qian SB, Hengel H et al (2012) Decoding human cytomegalovirus. Science 338:1088–1093PubMedCrossRef
5.
Roy S, Arav-Boger R (2014) New cell-signaling pathways for controlling cytomegalovirus replication. Am J Transplant 14:1249–1258PubMedCrossRef
6.
Dziurzynski K, Chang SM, Heimberger AB, Kalejta RF, McGregor Dallas SR, Smit M, Soroceanu L, Cobbs CS (2012) Consensus on the role of human cytomegalovirus in glioblastoma. Neuro-Oncology 14:246–255PubMedCrossRefPubMedCentral
7.
Tavalai N, Stamminger T (2008) New insights into the role of the subnuclear structure ND10 for viral infection. Biochim Biophys Acta 1783:2207–2221PubMedCrossRef
8.
Jackson SE, Mason GM, Wills MR (2011) Human cytomegalovirus immunity and immune evasion. Virus Res 157:151–160PubMedCrossRef
9.
Zhu H, Cong JP, Shenk T (1997) Use of differential display analysis to assess the effect of human cytomegalovirus infection on the accumulation of cellular RNAs: induction of interferon-responsive RNAs. Proc Natl Acad Sci U S A 94:13985–13990PubMedCrossRefPubMedCentral
10.
Liang P, Pardee AB (1992) Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257:967–971PubMedCrossRef
11.
Zhu H, Cong JP, Mamtora G, Gingeras T, Shenk T (1998) Cellular gene expression altered by human cytomegalovirus: global monitoring with oligonucleotide arrays. Proc Natl Acad Sci U S A 95:14470–14475PubMedCrossRefPubMedCentral
12.
Kenzelmann M, Muhlemann K (2000) Transcriptome analysis of fibroblast cells immediate-early after human cytomegalovirus infection. J Mol Biol 304:741–751PubMedCrossRef
13.
14.
Browne EP, Wing B, Coleman D, Shenk T (2001) Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: viral block to the accumulation of antiviral mRNAs. J Virol 75:12319–12330PubMedCrossRefPubMedCentral
15.
Simmen KA, Singh J, Luukkonen BG, Lopper M, Bittner A, Miller NE, Jackson MR, Compton T, Fruh K (2001) Global modulation of cellular transcription by human cytomegalovirus is initiated by viral glycoprotein B. Proc Natl Acad Sci U S A 98:7140–7145PubMedCrossRefPubMedCentral
16.
Song YJ, Stinski MF (2002) Effect of the human cytomegalovirus IE86 protein on expression of E2F-responsive genes: a DNA microarray analysis. Proc Natl Acad Sci U S A 99:2836–2841PubMedCrossRefPubMedCentral
17.
Hertel L, Mocarski ES (2004) Global analysis of host cell gene expression late during cytomegalovirus infection reveals extensive dysregulation of cell cycle gene expression and induction of pseudomitosis independent of US28 function. J Virol 78:11988–12011PubMedCrossRefPubMedCentral
18.
Juranic Lisnic V, Babic Cac M, Lisnic B, Trsan T, Mefferd A, Das Mukhopadhyay C, Cook CH, Jonjic S, Trgovcich J (2013) Dual analysis of the murine cytomegalovirus and host cell transcriptomes reveal new aspects of the virus-host cell interface. PLoS Pathog 9:e1003611PubMedCrossRefPubMedCentral
19.
Marcinowski L, Lidschreiber M, Windhager L, Rieder M, Bosse JB, Radle B, Bonfert T, Gyory I, de Graaf M, Prazeres da Costa O et al (2012) Real-time transcriptional profiling of cellular and viral gene expression during lytic cytomegalovirus infection. PLoS Pathog 8:e1002908PubMedCrossRefPubMedCentral
20.
McKinney C, Zavadil J, Bianco C, Shiflett L, Brown S, Mohr I (2014) Global reprogramming of the cellular translational landscape facilitates cytomegalovirus replication. Cell Rep 6:9–17PubMedCrossRef
21.
22.
23.
Stinski MF (1977) Synthesis of proteins and glycoproteins in cells infected with human cytomegalovirus. J Virol 23:751–767PubMedPubMedCentral
24.
de Sousa Abreu R, Penalva LO, Marcotte EM, Vogel C (2009) Global signatures of protein and mRNA expression levels. Mol BioSyst 5:1512–1526PubMed
25.
Gygi SP, Rochon Y, Franza BR, Aebersold R (1999) Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 19:1720–1730PubMedPubMedCentral
26.
Stanton RJ, McSharry BP, Rickards CR, Wang EC, Tomasec P, Wilkinson GW (2007) Cytomegalovirus destruction of focal adhesions revealed in a high-throughput Western blot analysis of cellular protein expression. J Virol 81:7860–7872PubMedCrossRefPubMedCentral
27.
Karlas A, Machuy N, Shin Y, Pleissner KP, Artarini A, Heuer D, Becker D, Khalil H, Ogilvie LA, Hess S et al (2010) Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 463:818–822PubMedCrossRef
28.
Krishnan MN, Ng A, Sukumaran B, Gilfoy FD, Uchil PD, Sultana H, Brass AL, Adametz R, Tsui M, Qian F et al (2008) RNA interference screen for human genes associated with West Nile virus infection. Nature 455:242–245PubMedCrossRefPubMedCentral
29.
Dumortier J, Streblow DN, Moses AV, Jacobs JM, Kreklywich CN, Camp D, Smith RD, Orloff SL, Nelson JA (2008) Human cytomegalovirus secretome contains factors that induce angiogenesis and wound healing. J Virol 82:6524–6535PubMedCrossRefPubMedCentral
30.
Weekes MP, Tan SY, Poole E, Talbot S, Antrobus R, Smith DL, Montag C, Gygi SP, Sinclair JH, Lehner PJ (2013) Latency-associated degradation of the MRP1 drug transporter during latent human cytomegalovirus infection. Science 340:199–202PubMedCrossRefPubMedCentral
31.
Le VT, Trilling M, Hengel H (2011) The cytomegaloviral protein pUL138 acts as potentiator of tumor necrosis factor (TNF) receptor 1 surface density to enhance ULb′-encoded modulation of TNF-alpha signaling. J Virol 85:13260–13270PubMedCrossRefPubMedCentral
32.
Montag C, Wagner JA, Gruska I, Vetter B, Wiebusch L, Hagemeier C (2011) The latency-associated UL138 gene product of human cytomegalovirus sensitizes cells to tumor necrosis factor alpha (TNF-alpha) signaling by upregulating TNF-alpha receptor 1 cell surface expression. J Virol 85:11409–11421PubMedCrossRefPubMedCentral
33.
Reyda S, Buscher N, Tenzer S, Plachter B (2014) Proteomic analyses of human cytomegalovirus strain AD169 derivatives reveal highly conserved patterns of viral and cellular proteins in infected fibroblasts. Viruses 6:172–188PubMedCrossRefPubMedCentral
34.
Weekes MP, Tomasec P, Huttlin EL, Fielding CA, Nusinow D, Stanton RJ, Wang EC, Aicheler R, Murrell I, Wilkinson GW et al (2014) Quantitative temporal viromics: an approach to investigate host-pathogen interaction. Cell 157:1460–1472PubMedCrossRefPubMedCentral
35.
Amsler L, Verweij MC, DeFilippis VR (2013) The tiers and dimensions of evasion of the type I interferon response by human cytomegalovirus. J Mol Biol 425:4857–4871PubMedCrossRef
36.
Koyuncu E, Purdy JG, Rabinowitz JD, Shenk T (2013) Saturated very long chain fatty acids are required for the production of infectious human cytomegalovirus progeny. PLoS Pathog 9:e1003333PubMedCrossRefPubMedCentral
37.
Angelova M, Zwezdaryk K, Ferris M, Shan B, Morris CA, Sullivan DE (2012) Human cytomegalovirus infection dysregulates the canonical Wnt/beta-catenin signaling pathway. PLoS Pathog 8:e1002959PubMedCrossRefPubMedCentral
38.
O’Connor C, DiMaggio PA Jr, Shenk T, Garcia BA (2014) Quantitative proteomic discovery of dynamic epigenome changes that control human cytomegalovirus infection. Mol Cell Proteomics
39.
Terry LJ, Vastag L, Rabinowitz JD, Shenk T (2012) Human kinome profiling identifies a requirement for AMP-activated protein kinase during human cytomegalovirus infection. Proc Natl Acad Sci U S A 109:3071–3076PubMedCrossRefPubMedCentral
40.
Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785PubMedCrossRef
41.
Yu Y, Maguire TG, Alwine JC (2011) Human cytomegalovirus activates glucose transporter 4 expression to increase glucose uptake during infection. J Virol 85:1573–1580PubMedCrossRefPubMedCentral
42.
Zhang A, Williamson CD, Wong DS, Bullough MD, Brown KJ, Hathout Y, Colberg-Poley AM (2011) Quantitative proteomic analyses of human cytomegalovirus-induced restructuring of endoplasmic reticulum-mitochondrial contacts at late times of infection. Mol Cell Proteomics 10(M111):009936PubMed
43.
Moorman NJ, Cristea IM, Terhune SS, Rout MP, Chait BT, Shenk T (2008) Human cytomegalovirus protein UL38 inhibits host cell stress responses by antagonizing the tuberous sclerosis protein complex. Cell Host Microbe 3:253–262PubMedCrossRefPubMedCentral
44.
Moorman NJ, Sharon-Friling R, Shenk T, Cristea IM (2010) A targeted spatial-temporal proteomics approach implicates multiple cellular trafficking pathways in human cytomegalovirus virion maturation. Mol Cell Proteomics 9:851–860PubMedCrossRefPubMedCentral
45.
Milbradt J, Kraut A, Hutterer C, Sonntag E, Schmeiser C, Ferro M, Wagner S, Lenac T, Claus C, Pinkert S et al (2014) Proteomic analysis of the multimeric nuclear egress complex of human cytomegalovirus. Mol Cell Proteomics 13(8):2132–2146PubMedCrossRef
46.
Munger J, Bajad SU, Coller HA, Shenk T, Rabinowitz JD (2006) Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog 2:e132PubMedCrossRefPubMedCentral
47.
Munger J, Bennett BD, Parikh A, Feng XJ, McArdle J, Rabitz HA, Shenk T, Rabinowitz JD (2008) Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Nat Biotechnol 26:1179–1186PubMedCrossRefPubMedCentral
48.
Liu ST, Sharon-Friling R, Ivanova P, Milne SB, Myers DS, Rabinowitz JD, Brown HA, Shenk T (2011) Synaptic vesicle-like lipidome of human cytomegalovirus virions reveals a role for SNARE machinery in virion egress. Proc Natl Acad Sci U S A 108:12869–12874PubMedCrossRefPubMedCentral
49.
Weisblum Y, Panet A, Zakay-Rones Z, Haimov-Kochman R, Goldman-Wohl D, Ariel I, Falk H, Natanson-Yaron S, Goldberg MD, Gilad R et al (2011) Modeling of human cytomegalovirus maternal-fetal transmission in a novel decidual organ culture. J Virol 85:13204–13213PubMedCrossRefPubMedCentral
50.
Smith MS, Goldman DC, Bailey AS, Pfaffle DL, Kreklywich CN, Spencer DB, Othieno FA, Streblow DN, Garcia JV, Fleming WH et al (2010) Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model. Cell Host Microbe 8:284–291PubMedCrossRefPubMedCentral
51.
Jager S, Cimermancic P, Gulbahce N, Johnson JR, McGovern KE, Clarke SC, Shales M, Mercenne G, Pache L, Li K et al (2012) Global landscape of HIV-human protein complexes. Nature 481:365–370
52.
Boone C, Bussey H, Andrews BJ (2007) Exploring genetic interactions and networks with yeast. Nat Rev Genet 8:437–449PubMedCrossRef
53.
Bassik MC, Kampmann M, Lebbink RJ, Wang S, Hein MY, Poser I, Weibezahn J, Horlbeck MA, Chen S, Mann M et al (2013) A systematic mammalian genetic interaction map reveals pathways underlying ricin susceptibility. Cell 152:909–922PubMedCrossRefPubMedCentral
54.
Laufer C, Fischer B, Billmann M, Huber W, Boutros M (2013) Mapping genetic interactions in human cancer cells with RNAi and multiparametric phenotyping. Nat Methods 10:427–431PubMedCrossRef
55.
56.
Goodrum FD, Jordan CT, High K, Shenk T (2002) Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells: a model for latency. Proc Natl Acad Sci U S A 99:16255–16260PubMedCrossRefPubMedCentral
57.
Hahn G, Jores R, Mocarski ES (1998) Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc Natl Acad Sci U S A 95:3937–3942PubMedCrossRefPubMedCentral
58.
59.
Huang MM, Kew VG, Jestice K, Wills MR, Reeves MB (2012) Efficient human cytomegalovirus reactivation is maturation dependent in the Langerhans dendritic cell lineage and can be studied using a CD14+ experimental latency model. J Virol 86:8507–8515PubMedCrossRefPubMedCentral
60.
Reeves MB, Lehner PJ, Sissons JG, Sinclair JH (2005) An in vitro model for the regulation of human cytomegalovirus latency and reactivation in dendritic cells by chromatin remodelling. J Gen Virol 86:2949–2954PubMedCrossRef
Metadata
Title
Manipulation of host pathways by human cytomegalovirus: insights from genome-wide studies
Authors
Yifat Cohen
Noam Stern-Ginossar
Publication date
01-11-2014
Publisher
Springer Berlin Heidelberg
Published in
Seminars in Immunopathology / Issue 6/2014
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-014-0443-7

Other articles of this Issue 6/2014

Seminars in Immunopathology 6/2014 Go to the issue

INTRODUCTION

Editorial introduction for Seminars in Immunopathology special issue on “Immune modulation, properties and models of CMV”

Review

The use of microRNA by human viruses: lessons from NK cells and HCMV infection

Review

MCMV avoidance of recognition and control by NK cells

Review

CMV-encoded Fcγ receptors: modulators at the interface of innate and adaptive immunity

Review

Models of vertical cytomegalovirus (CMV) transmission and pathogenesis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits