REVIEW crossm Human Parvoviruses Jianming Qiu,a Maria Söderlund-Venermo,b Neal S. Youngc Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Downloaded from Kansas City, Kansas, USAa; Department of Virology, University of Helsinki, Helsinki, Finlandb; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USAc SUMMARY .......................................................................................44 Published 2 November 2016 INTRODUCTION .................................................................................44 Citation Qiu J, Söderlund-Venermo M, Young VIRUS TAXONOMY .............................................................................45 NS. 2017. Human parvoviruses. Clin Microbiol BASIC VIROLOGY ...............................................................................45 Rev 30:43–113. https://doi.org/10.1128/ Virus Structure.................................................................................45 CMR.00040-16. http://cmr.asm.org/ B19V Genome Organization and Expression ................................................46 B19V genome and infectious clones......................................................46 Copyright © 2016 American Society for B19V transcription ..........................................................................48 Microbiology. All Rights Reserved. B19V gene expression regulation .........................................................48 Address correspondence to Jianming Qiu, (i) Internal polyadenylation controls production of VP- and 11-kDa protein- [email protected]. encoding mRNAs......................................................................48 (ii) Multiple splicing enhancers function to define the central exon of B19V pre- mRNA splicing.........................................................................48 B19V proteins ...............................................................................49 B19V Tropism and Entry......................................................................51 on November 2, 2016 by University of Kansas B19V cell culture............................................................................51 B19V receptor and coreceptors ...........................................................51 B19V entry and the role of B19V VP1u in virus entry ...................................51 B19V Replication ..............................................................................52 Elements involved in B19V DNA replication both in cis and in trans ..................52 Cellular control of B19V DNA replication .................................................52 (i) S-phase-dependent viral DNA replication...........................................52 (ii) Epo-dependent B19V DNA replication .............................................52 (iii) Hypoxia-facilitated B19V replication ...............................................53 HBoV1 Biology.................................................................................53 HBoV1 genome and infectious clone .....................................................53 HBoV1 gene transcription and regulation ................................................53 HBoV1 cell culture..........................................................................55 Cellular control of HBoV1 DNA replication ...............................................55 HOST CELL RESPONSE AND PATHOGENESIS ...............................................56 Cellular Response to Productive B19V Infection ............................................56 B19V infection-induced DNA damage response .........................................56 B19V infection-induced cell cycle arrest ..................................................56 B19V infection-induced erythroid cell death .............................................56 Cellular Response to Unproductive B19V Infection.........................................57 B19V infection of endothelial cells ........................................................57 B19V infection in other tissues ............................................................58 Airway Epithelium Damage Caused by HBoV1 Infection...................................58 EPIDEMIOLOGY .................................................................................58 Virus Prevalence and Transmission ..........................................................58 B19V .........................................................................................58 HBoV.........................................................................................60 Genotypes and Molecular Epidemiology ....................................................61 B19V .........................................................................................61 HBoV.........................................................................................61 IMMUNE RESPONSE ............................................................................62 Adaptive Immune Response .................................................................62 Humoral immune response to B19V infection ...........................................62 Cellular immunity to B19V infection ......................................................62 Humoral and cellular immune response to HBoV1 infection ...........................63 (continued) January 2017 Volume 30 Issue 1 Clinical Microbiology Reviews cmr.asm.org 43 Qiu et al. Clinical Microbiology Reviews (i) Humoral immune response ..........................................................63 (ii) Cellular immune response...........................................................63 Innate Immunity...............................................................................63 Innate immunity to B19V infection .......................................................63 Innate immunity to HBoV1 infection......................................................63 CLINICAL MANIFESTATIONS...................................................................64 Diseases Caused by B19V Infection..........................................................64 Erythema infectiosum ......................................................................64 B19V arthropathy...........................................................................65 Hydrops fetalis..............................................................................66 (i) Pregnancy risks .......................................................................66 (ii) Pathogenesis .........................................................................67 Downloaded from (iii) Diagnosis .............................................................................67 (iv) Treatment ............................................................................67 (v) Congenital infection .................................................................67 Transient aplastic crisis (TAC)..............................................................68 Persistent infection and pure red blood cell aplasia ....................................69 B19V infection and malaria ................................................................70 Other hematological syndromes linked to B19V.........................................70 Encephalitis and other neurological syndromes .........................................71 Myocarditis and other heart diseases.....................................................71 Hepatitis and other liver diseases .........................................................72 http://cmr.asm.org/ B19V and autoimmune/immune-mediated diseases.....................................72 B19V and kidney disease ..................................................................73 Other associations ..........................................................................73 Diseases Associated with HBoV Infection ...................................................73 Respiratory tract infections ................................................................73 Diseases associated with HBoV2 to HBoV4...............................................75 LABORATORY DIAGNOSTICS ..................................................................75 B19V Serology .................................................................................75 B19V Nucleic Acid Testing....................................................................77 B19V Antigen Assays..........................................................................77 on November 2, 2016 by University of Kansas HBoV Laboratory Diagnosis ..................................................................77 TREATMENT AND PREVENTION...............................................................78 OTHER EMERGING HUMAN PARVOVIRUSES ................................................79 Human Parvovirus 4 ..........................................................................79 Human Bufavirus ..............................................................................81 FUTURE DIRECTIONS ...........................................................................81 Disease Validation and Animal Models......................................................81 Antiviral Drug Development .................................................................81 ACKNOWLEDGMENTS ..........................................................................82 REFERENCES .....................................................................................82 AUTHOR BIOS..................................................................................113