Citations to this article

Cytomegalovirus: pathogen, paradigm, and puzzle
Michael Boeckh, Adam P. Geballe
Michael Boeckh, Adam P. Geballe
Published May 2, 2011
Citation Information: J Clin Invest. 2011;121(5):1673-1680. https://doi.org/10.1172/JCI45449.
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Cytomegalovirus: pathogen, paradigm, and puzzle

Abstract

Human cytomegalovirus (CMV), one of the eight herpesviruses that commonly infect humans, is best known for its propensity to cause disease in immunocompromised patients, especially transplant recipients, patients with advanced AIDS, and congenitally infected newborns. Advances in molecular virology coupled with improvements in diagnostic methods and treatment options have vastly improved our understanding of and ability to manage CMV, but many uncertainties remain, including the mechanisms of persistence and pathogenesis and its hypothesized roles in a variety of human illnesses. Here we review recent advances that are reshaping our view and approach to this fascinating virus.

Authors

Michael Boeckh, Adam P. Geballe

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Human Cytomegalovirus Immediate-Early 1 Protein Rewires Upstream STAT3 to Downstream STAT1 Signaling Switching an IL6-Type to an IFNγ-Like Response
T Harwardt, S Lukas, M Zenger, T Reitberger, D Danzer, T Übner, DC Munday, M Nevels, C Paulus, RF Kalejta 		PLoS pathogens 2016
Transcriptome altered by latent human cytomegalovirus infection on THP-1 cells using RNA-seq
Q Zhang, MM Lai, YY Lou, BH Guo, HY Wang, XQ Zheng 		Gene 2016
Utility of the Enzyme-Linked Immunospot Interferon-γ–Release Assay to Predict the Risk of Cytomegalovirus Infection in Hematopoietic Cell Transplant Recipients
L Nesher, DP Shah, EJ Ariza-Heredia, JM Azzi, HK Siddiqui, SS Ghantoji, LY Marsh, L Michailidis, G Makedonas, K Rezvani, EJ Shpall, RF Chemaly 		The Journal of Infectious Diseases 2016
The Honolulu Liver Disease Cluster at the Medical Center: Its Mysteries and Challenges
R Teschke, A Eickhoff 		International journal of molecular sciences 2016
Cytomegalovirus related fatal duodenal diverticular bleeding: Case report and literature review
J Makker, B Bajantri, S Sakam, S Chilimuri 		World journal of gastroenterology : WJG 2016
Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape
S Landolfo, MD Andrea, V DellOste, F Gugliesi 		World Journal of Virology 2016
Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway
TJ Gardner, D Tortorella 		Microbiology and molecular biology reviews : MMBR 2016
Approved Antiviral Drugs over the Past 50 Years
ED Clercq, G Li 		Clinical microbiology reviews 2016
Human Cytomegalovirus Latency: Approaching the Gordian Knot
F Goodrum 		Annual Review of Virology 2016
Clinical utility of bronchoalveolar lavage cytomegalovirus viral loads in the diagnosis of cytomegalovirus pneumonitis in infants: Utility of BAL CMV Viral Load in Infant CMV Pneumonitis
K Govender, P Jeena, R Parboosing 		Journal of Medical Virology 2016
Clinical significance of the single nucleotide polymorphism TLR2 R753Q in heart transplant recipients at risk for cytomegalovirus disease
M Schneider, T Matiqi, M Kundi, FJ Rieder, M Andreas, R Strassl, A Zuckermann, C Jungbauer, C Steininger 		Journal of Clinical Virology 2016
Diagnostic moléculaire du Cytomégalovirus (CMV), de l’herpès virus humain de type 6 (HHV6) et d’Epstein-Barr virus (EBV) par PCR en temps réel chez les femmes enceintes VIH séropositives et séronégatives à Ouagadougou, Burkina Faso
AR Ouedraogo, M Kabre, C Bisseye, TM Zohoncon, M Asshi, ST Soubeiga, B Diarra, L Traore, FW Djigma, D Ouermi, V Pietra, N Barro, J Simporé 		The Pan African medical journal 2016
Additive Protection against Congenital Cytomegalovirus Conferred by Combined Glycoprotein B/pp65 Vaccination Using a Lymphocytic Choriomeningitis Virus Vector
MR Schleiss, U Berka, E Watson, M Aistleithner, B Kiefmann, B Mangeat, EC Swanson, PA Gillis, N Hernandez-Alvarado, C Fernández-Alarcón, JC Zabeli, DD Pinschewer, AE Lilja, M Schwendinger, F Guirakhoo, TP Monath, KK Orlinger, KM Edwards 		Clinical and vaccine immunology : CVI 2016
Long and Short Isoforms of the Human Cytomegalovirus UL138 Protein Silence IE Transcription and Promote Latency
SH Lee, K Caviness, ER Albright, JH Lee, CB Gelbmann, M Rak, F Goodrum, RF Kalejta, RM Sandri-Goldin 		Journal of virology 2016
Current concepts in the prevention of pathogen transmission via blood/plasma-derived products for bleeding disorders
GD Minno, CF Perno, A Tiede, D Navarro, M Canaro, L Güertler, JW Ironside 		Blood Reviews 2016
Human cytomegalovirus and transplantation: drug development and regulatory issues
McIntosh M, Hauschild B, Miller V 		Journal of Virus Eradication 2016
A Diverse Repertoire of CD4 T Cells Targets the Immediate-Early 1 Protein of Human Cytomegalovirus
S Ameres, X Liang, M Wiesner, J Mautner, A Moosmann 		Frontiers in immunology 2015
High-Throughput Analysis of Human Cytomegalovirus Genome Diversity Highlights the Widespread Occurrence of Gene-Disrupting Mutations and Pervasive Recombination
S Sijmons, K Thys, MM Ngwese, EV Damme, J Dvorak, MV Loock, G Li, R Tachezy, L Busson, J Aerssens, MV Ranst, P Maes, L Hutt-Fletcher 		Journal of virology 2015
Development of a high-content screen for the identification of inhibitors directed against the early steps of the cytomegalovirus infectious cycle
TJ Gardner, T Cohen, V Redmann, Z Lau, D Felsenfeld, D Tortorella 		Antiviral Research 2015
The Human Cytomegalovirus UL133-138 Gene Locus Attenuates the Lytic Viral Cycle in Fibroblasts
N Dutta, P Lashmit, J Yuan, J Meier, MF Stinski, AJ Sinclair 		PloS one 2015
RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production
N Goulidaki, S Alarifi, SH Alkahtani, A Al-Qahtani, DA Spandidos, C Stournaras, G Sourvinos 		Cell cycle (Georgetown, Tex.) 2015
Comparison of monovalent glycoprotein B with bivalent gB/pp65 (GP83) vaccine for congenital cytomegalovirus infection in a guinea pig model: Inclusion of GP83 reduces gB antibody response but both vaccine approaches provide equivalent protection against pup mortality
EC Swanson, P Gillis, N Hernandez-Alvarado, C Fernández-Alarcón, M Schmit, JC Zabeli, F Wussow, DJ Diamond, MR Schleiss 		Vaccine 2015
Cytomegalovirus infection in transplant recipients
LS Azevedo, LC Pierrotti, E Abdala, SF Costa, TM Strabelli, SV Campos, JF Ramos, AZ Latif, N Litvinov, NZ Maluf, HH Filho, CS Pannuti, MH Lopes, VA Santos, CC Linardi, MA Yasuda, HH Marques 		Clinics 2015
Human Cytomegalovirus UL135 and UL136 Genes Are Required for Postentry Tropism in Endothelial Cells
F Bughio, M Umashankar, J Wilson, F Goodrum, RM Sandri-Goldin 		Journal of virology 2015
Control of Murine Cytomegalovirus Infection by γδ T Cells
S Sell, M Dietz, A Schneider, R Holtappels, M Mach, TH Winkler, SC Jameson 		PLoS pathogens 2015
Vaccination with a Live Attenuated Cytomegalovirus Devoid of a Protein Kinase R Inhibitory Gene Results in Reduced Maternal Viremia and Improved Pregnancy Outcome in a Guinea Pig Congenital Infection Model
MR Schleiss, CJ Bierle, EC Swanson, MA McVoy, JB Wang, Z Al-Mahdi, AP Geballe, K Frueh 		Journal of virology 2015
Cellular defense against latent colonization foiled by human cytomegalovirus UL138 protein
SH Lee, ER Albright, JH Lee, D Jacobs, RF Kalejta 		Science Advances 2015
Differentiation-Coupled Induction of Human Cytomegalovirus Replication by Union of the Major Enhancer Retinoic Acid, Cyclic AMP, and NF-κB Response Elements
J Yuan, M Li, YR Torres, CS Galle, JL Meier, K Frueh 		Journal of virology 2015
Functional annotation of human cytomegalovirus gene products: an update
EV Damme, MV Loock 		Frontiers in microbiology 2014
Genomic and Functional Characteristics of Human Cytomegalovirus Revealed by Next-Generation Sequencing
S Sijmons, MV Ranst, P Maes 		Viruses 2014
Increased numbers and functional activity of CD56 + T cells in healthy cytomegalovirus positive subjects
M Almehmadi, BF Flanagan, N Khan, S Alomar, SE Christmas 		Immunology 2014
Myopericarditis complicated by pulmonary embolism in an immunocompetent patient with acute cytomegalovirus infection: a case report
Y Vandamme, A Ducancelle, L Biere, N Viot, F Rouleau, V Delbos, P Abgueguen 		BMC Research Notes 2014
HCMV Infection of Humanized Mice after Transplantation of G-CSF–Mobilized Peripheral Blood Stem Cells from HCMV-Seropositive Donors
M Hakki, DC Goldman, DN Streblow, KL Hamlin, CN Krekylwich, WH Fleming, JA Nelson 		Biology of Blood and Marrow Transplantation 2014
The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection
G Sourvinos, A Morou, I Sanidas, I Codruta, SA Ezell, C Doxaki, SC Kampranis, F Kottakis, PN Tsichlis 		PLoS pathogens 2014
An adjuvanted inactivated murine cytomegalovirus (MCMV) vaccine induces potent and long-term protective immunity against a lethal challenge with virulent MCMV
H Wang, Y Yao, C Huang, X Fu, Q Chen, H Zhang, J Chen, F Fang, Z Xie, Z Chen 		BMC Infectious Diseases 2014
Human Cytomegalovirus Antigens in Malignant Gliomas as Targets for Adoptive Cellular Therapy
D Landi, M Hegde, N Ahmed 		Frontiers in Oncology 2014
Lack of XBP-1 Impedes Murine Cytomegalovirus Gene Expression
A Drori, M Messerle, W Brune, B Tirosh, M Nevels 		PloS one 2014
Antagonistic Determinants Controlling Replicative and Latent States of Human Cytomegalovirus Infection
M Umashankar, M Rak, F Bughio, P Zagallo, K Caviness, FD Goodrum 		Journal of virology 2014
Complex Expression of the UL136 Gene of Human Cytomegalovirus Results in Multiple Protein Isoforms with Unique Roles in Replication
K Caviness, L Cicchini, M Rak, M Umashankar, F Goodrum 		Journal of virology 2014
Naïve and memory CD8 T cell pool homeostasis in advanced aging: impact of age and of antigen-specific responses to cytomegalovirus
R Vescovini, FF Fagnoni, AR Telera, L Bucci, M Pedrazzoni, F Magalini, A Stella, F Pasin, MC Medici, A Calderaro, R Volpi, D Monti, C Franceschi, J Nikolich-Žugich, P Sansoni 		AGE 2013
Developing a Vaccine against Congenital Cytomegalovirus (CMV) Infection: What Have We Learned from Animal Models? Where Should We Go Next?
MR Schleiss 		Future Virology 2013
Immunization with cytomegalovirus envelope glycoprotein M and glycoprotein N DNA vaccines can provide mice with complete protection against a lethal murine cytomegalovirus challenge
H Wang, Y Yao, C Huang, Q Chen, J Chen, Z Chen 		Virologica Sinica 2013
Prevalence of Cytomegalovirus DNA in Cord Blood and Voided Urine Obtained from Pregnant Women at the End of Pregnancy
R Al-Awadhi, J Al-Harmi, S AlFadhli 		Medical Principles and Practice 2013
Nucleosome maps of the human cytomegalovirus genome reveal a temporal switch in chromatin organization linked to a major IE protein
E Zalckvar, C Paulus, D Tillo, A Asbach-Nitzsche, Y Lubling, C Winterling, N Strieder, K Mucke, F Goodrum, E Segal, M Nevels 		Proceedings of the National Academy of Sciences 2013
Presentation of an immunodominant immediate-early CD8+ T cell epitope resists human cytomegalovirus immunoevasion
S Ameres, J Mautner, F Schlott, M Neuenhahn, DH Busch, B Plachter, A Moosmann 		PLoS pathogens 2013
Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial
L Smith, M Wloch, J Chaplin, M Gerber, A Rolland 		Human vaccines 2013
Cytomegalovirus infections in solid organ transplantation: a review
P Ramanan, RR Razonable 		Infection & Chemotherapy 2013
Dual analysis of the murine cytomegalovirus and host cell transcriptomes reveal new aspects of the virus-host cell interface
VJ Lisnic, MB Cac, B Lisnic, T Trsan, A Mefferd, CD Mukhopadhyay, CH Cook, S Jonjic, J Trgovcich 		PLoS pathogens 2013
Detection of cytomegalovirus drug resistance mutations by next-generation sequencing
MK Sahoo, MI Lefterova, F Yamamoto, JJ Waggoner, S Chou, SP Holmes, MW Anderson, BA Pinsky 		Journal of clinical microbiology 2013
Myeloblastic cell lines mimic some but not all aspects of human cytomegalovirus experimental latency defined in primary CD34+ cell populations
ER Albright, RF Kalejta 		Journal of virology 2013
Age-associated alterations in γδ T-cells are present predominantly in individuals infected with Cytomegalovirus
K Wistuba-Hamprecht, D Frasca, B Blomberg, G Pawelec, E Derhovanessian 		Immunity & Ageing 2013
An endothelial cell-specific requirement for the UL133-UL138 locus of human cytomegalovirus for efficient virus maturation
F Bughio, DA Elliott, F Goodrum 		Journal of virology 2013
Letermovir Treatment of Human Cytomegalovirus Infection Antiinfective Agent
Verghese PS, Schleiss MR 		Drugs of the future 2013
Human cytomegalovirus persistence
F Goodrum, K Caviness, P Zagallo 		Cellular Microbiology 2012
Tale of a tegument transactivator: the past, present and future of human CMV pp71
RR Penkert, RF Kalejta 		Future Virology 2012
Histone H3 lysine 4 methylation marks postreplicative human cytomegalovirus chromatin
A Nitzsche, C Steinhäusser, K Mücke, C Paulus, M Nevels 		Journal of virology 2012
Enterocolitis with multiple ulcers of ileum and right colon in a patient with leukaemia attributed to cytomegalovirus
IN Papadopoulos, I Konstantiadou, E Papantoni 		BMJ case reports 2012
Interactions between Proteins Encoded within the Human Cytomegalovirus UL133-UL138 Locus
A Petrucelli, M Umashankar, P Zagallo, M Rak, F Goodrum 		Journal of virology 2012
Human Cytomegalovirus Infant Infection Adversely Affects Growth and Development in Maternally HIV-Exposed and Unexposed Infants in Zambia
Gompels UA, Larke N, Sanz-Ramos M, Bates M, Musonda K, Manno D, Siame J, Monze M, Filteau S 		Clinical Infectious Diseases 2012
β-HHVs and HHV-8 in Lymphoproliferative Disorders
C Quadrelli, P Barozzi, G Riva, D Vallerini, E Zanetti, L Potenza, F Forghieri, M Luppi 		Mediterranean journal of hematology and infectious diseases 2011
Human cytomegalovirus infection and atherothrombosis
M Popović, K Smiljanić, B Dobutović, T Syrovets, T Simmet, ER Isenović 		Journal of Thrombosis and Thrombolysis 2011
Resistance to maribavir is associated with the exclusion of pUL27 from nucleoli during human cytomegalovirus infection
M Hakki, C Drummond, B Houser, G Marousek, S Chou 		Antiviral Research 2011
The biology of cytomegalovirus drug resistance
M Hakki, S Chou 		Current Opinion in Infectious Diseases 2011
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd 		Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009

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