Microbiology, epidemiology, and pathogenesis of parvovirus B19 infection
- Jeanne A Jordan, PhD
Jeanne A Jordan, PhD
- School of Public Health
- The George Washington University
- Section Editors
- Martin S Hirsch, MD
Martin S Hirsch, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Viral Infections
- Professor of Medicine
- Harvard Medical School
- Morven S Edwards, MD
Morven S Edwards, MD
- Section Editor — Pediatric Infectious Diseases
- Professor of Pediatrics
- Baylor College of Medicine
The Parvoviridae family contains two subfamilies: Parvovirinae, which infect mammals and birds, and Densovirinae, which infect arthropods. The Parvovirinae subfamily has been subdivided into eight genera: Erythroparvovirus, Dependoparvovirus, Protoparvovirus, Amdoparvovirus, Bocaparvovirus, Aveparvovirus, Copiparvovirus, and Tetraparvovirus . The focus here will be limited to Erythroparvovirus genera, and mainly to human parvovirus B19 (B19 prototype strain); only brief coverage will be given to the less common genotype 2 (prototype strain: LaLi) and genotype 3 (prototype strain: V9) genera within this subfamily .
Unless otherwise specified, parvovirus B19 will be the strain referred to when describing epidemiology and transmission, which are discussed in this topic. The spectrum of disease manifestations, diagnosis, treatment, and prevention of parvovirus B19 are discussed elsewhere. (See "Clinical manifestations and diagnosis of parvovirus B19 infection" and "Treatment and prevention of parvovirus B19 infection".)
Classification — There are three genotypes within the Erythroparvovirus genus. Parvovirus B19 is the predominant parvovirus pathogen in humans and the prototype genotype 1 strain. Genotype 2 (prototype strain, LaLi) and genotype 3 (prototype strain, V9) are less common and more recently described [3-5]. Genotypes 1 and 2 are typically found in western countries (eg, United States and Europe), while genotype 3 circulates primarily in sub-Saharan Africa and South America , but has been encountered in Europe and India. Compared with genotype 1, much less has been published on the transmission and epidemiology of genotype 2 and genotype 3. The nucleotide sequence differs among the three genotypes by 13 to 14 percent [5,7]. Not surprisingly, the divergence at the amino acid level among the three genotypes is significantly less than that seen at the nucleotide level.
Viral structure — Parvovirus B19 is a small (26 nm), non-enveloped, single stranded DNA (5.6-kb) virus. It is among the smallest of the DNA animal viruses. The linear genome encodes the following proteins:
●Two viral capsid proteins: a minor structural protein VP1 (781 amino acids [aa], 84 kDa) and a major structural protein VP2 (554 aa, 58 kDa). These are encoded by overlapping reading frames and are expressed during productive infection. The smaller VP2 protein constitutes 95 percent of the capsid while the larger VP1 protein makes up only 5 percent.
- Qiu J, Söderlund-Venermo M, Young NS. Human Parvoviruses. Clin Microbiol Rev 2017; 30:43.
- Brown KE. Variants of B19. Dev Biol (Basel) 2004; 118:71.
- Nguyen QT, Sifer C, Schneider V, et al. Novel human erythrovirus associated with transient aplastic anemia. J Clin Microbiol 1999; 37:2483.
- Nguyen QT, Wong S, Heegaard ED, Brown KE. Identification and characterization of a second novel human erythrovirus variant, A6. Virology 2002; 301:374.
- Servant A, Laperche S, Lallemand F, et al. Genetic diversity within human erythroviruses: identification of three genotypes. J Virol 2002; 76:9124.
- Parsyan A, Szmaragd C, Allain JP, Candotti D. Identification and genetic diversity of two human parvovirus B19 genotype 3 subtypes. J Gen Virol 2007; 88:428.
- Norja P, Eis-Hübinger AM, Söderlund-Venermo M, et al. Rapid sequence change and geographical spread of human parvovirus B19: comparison of B19 virus evolution in acute and persistent infections. J Virol 2008; 82:6427.
- Moffatt S, Yaegashi N, Tada K, et al. Human parvovirus B19 nonstructural (NS1) protein induces apoptosis in erythroid lineage cells. J Virol 1998; 72:3018.
- Jordan JA, Butchko AR. Apoptotic activity in villous trophoblast cells during B19 infection correlates with clinical outcome: assessment by the caspase-related M30 Cytodeath antibody. Placenta 2002; 23:547.
- Moffatt S, Tanaka N, Tada K, et al. A cytotoxic nonstructural protein, NS1, of human parvovirus B19 induces activation of interleukin-6 gene expression. J Virol 1996; 70:8485.
- Fu Y, Ishii KK, Munakata Y, et al. Regulation of tumor necrosis factor alpha promoter by human parvovirus B19 NS1 through activation of AP-1 and AP-2. J Virol 2002; 76:5395.
- Nakashima A, Morita E, Saito S, Sugamura K. Human Parvovirus B19 nonstructural protein transactivates the p21/WAF1 through Sp1. Virology 2004; 329:493.
- Kaufmann B, Simpson AA, Rossmann MG. The structure of human parvovirus B19. Proc Natl Acad Sci U S A 2004; 101:11628.
- Mortimer PP, Humphries RK, Moore JG, et al. A human parvovirus-like virus inhibits haematopoietic colony formation in vitro. Nature 1983; 302:426.
- Brown KE, Anderson SM, Young NS. Erythrocyte P antigen: cellular receptor for B19 parvovirus. Science 1993; 262:114.
- Brown KE, Hibbs JR, Gallinella G, et al. Resistance to parvovirus B19 infection due to lack of virus receptor (erythrocyte P antigen). N Engl J Med 1994; 330:1192.
- Jordan JA, DeLoia JA. Globoside expression within the human placenta. Placenta 1999; 20:103.
- Rouger P, Gane P, Salmon C. Tissue distribution of H, Lewis and P antigens as shown by a panel of 18 monoclonal antibodies. Rev Fr Transfus Immunohematol 1987; 30:699.
- Ozawa K, Ayub J, Kajigaya S, et al. The gene encoding the nonstructural protein of B19 (human) parvovirus may be lethal in transfected cells. J Virol 1988; 62:2884.
- Weigel-Kelley KA, Yoder MC, Srivastava A. Recombinant human parvovirus B19 vectors: erythrocyte P antigen is necessary but not sufficient for successful transduction of human hematopoietic cells. J Virol 2001; 75:4110.
- Weigel-Kelley KA, Yoder MC, Srivastava A. Alpha5beta1 integrin as a cellular coreceptor for human parvovirus B19: requirement of functional activation of beta1 integrin for viral entry. Blood 2003; 102:3927.
- Munakata Y, Saito-Ito T, Kumura-Ishii K, et al. Ku80 autoantigen as a cellular coreceptor for human parvovirus B19 infection. Blood 2005; 106:3449.
- Bönsch C, Zuercher C, Lieby P, et al. The globoside receptor triggers structural changes in the B19 virus capsid that facilitate virus internalization. J Virol 2010; 84:11737.
- Kühl U, Rohde M, Lassner D, et al. miRNA as activity markers in Parvo B19 associated heart disease. Herz 2012; 37:637.
- Naides SJ. Erythema infectiosum (fifth disease) occurrence in Iowa. Am J Public Health 1988; 78:1230.
- Serjeant GR, Serjeant BE, Thomas PW, et al. Human parvovirus infection in homozygous sickle cell disease. Lancet 1993; 341:1237.
- Yamashita K, Matsunaga Y, Taylor-Wiedeman J, Yamazaki S. A significant age shift of the human parvovirus B19 antibody prevalence among young adults in Japan observed in a decade. Jpn J Med Sci Biol 1992; 45:49.
- Cohen BJ, Gandhi J, Clewley JP. Genetic variants of parvovirus B19 identified in the United Kingdom: implications for diagnostic testing. J Clin Virol 2006; 36:152.
- Heegaard ED, Panum Jensen I, Christensen J. Novel PCR assay for differential detection and screening of erythrovirus B19 and erythrovirus V9. J Med Virol 2001; 65:362.
- Hokynar K, Söderlund-Venermo M, Pesonen M, et al. A new parvovirus genotype persistent in human skin. Virology 2002; 302:224.
- Bock CT, Düchting A, Utta F, et al. Molecular phenotypes of human parvovirus B19 in patients with myocarditis. World J Cardiol 2014; 6:183.
- Cohen BJ, Buckley MM. The prevalence of antibody to human parvovirus B19 in England and Wales. J Med Microbiol 1988; 25:151.
- Kerr S, O'Keeffe G, Kilty C, Doyle S. Undenatured parvovirus B19 antigens are essential for the accurate detection of parvovirus B19 IgG. J Med Virol 1999; 57:179.
- Koch WC, Adler SP. Human parvovirus B19 infections in women of childbearing age and within families. Pediatr Infect Dis J 1989; 8:83.
- Anderson LJ, Tsou C, Parker RA, et al. Detection of antibodies and antigens of human parvovirus B19 by enzyme-linked immunosorbent assay. J Clin Microbiol 1986; 24:522.
- Röhrer C, Gärtner B, Sauerbrei A, et al. Seroprevalence of parvovirus B19 in the German population. Epidemiol Infect 2008; 136:1564.
- Chorba T, Coccia P, Holman RC, et al. The role of parvovirus B19 in aplastic crisis and erythema infectiosum (fifth disease). J Infect Dis 1986; 154:383.
- Plummer FA, Hammond GW, Forward K, et al. An erythema infectiosum-like illness caused by human parvovirus infection. N Engl J Med 1985; 313:74.
- Anderson MJ, Higgins PG, Davis LR, et al. Experimental parvoviral infection in humans. J Infect Dis 1985; 152:257.
- Gillespie SM, Cartter ML, Asch S, et al. Occupational risk of human parvovirus B19 infection for school and day-care personnel during an outbreak of erythema infectiosum. JAMA 1990; 263:2061.
- Cartter ML, Farley TA, Rosengren S, et al. Occupational risk factors for infection with parvovirus B19 among pregnant women. J Infect Dis 1991; 163:282.
- Gay NJ, Hesketh LM, Cohen BJ, et al. Age specific antibody prevalence to parvovirus B19: how many women are infected in pregnancy? Commun Dis Rep CDR Rev 1994; 4:R104.
- Bell LM, Naides SJ, Stoffman P, et al. Human parvovirus B19 infection among hospital staff members after contact with infected patients. N Engl J Med 1989; 321:485.
- Harrison J, Jones CE. Human parvovirus B19 infection in healthcare workers. Occup Med (Lond) 1995; 45:93.
- Seng C, Watkins P, Morse D, et al. Parvovirus B19 outbreak on an adult ward. Epidemiol Infect 1994; 113:345.
- Dowell SF, Török TJ, Thorp JA, et al. Parvovirus B19 infection in hospital workers: community or hospital acquisition? J Infect Dis 1995; 172:1076.
- Ray SM, Erdman DD, Berschling JD, et al. Nosocomial exposure to parvovirus B19: low risk of transmission to healthcare workers. Infect Control Hosp Epidemiol 1997; 18:109.
- Jordan JA. Identification of human parvovirus B19 infection in idiopathic nonimmune hydrops fetalis. Am J Obstet Gynecol 1996; 174:37.
- Jordan J, Tiangco B, Kiss J, Koch W. Human parvovirus B19: prevalence of viral DNA in volunteer blood donors and clinical outcomes of transfusion recipients. Vox Sang 1998; 75:97.
- McOmish F, Yap PL, Jordan A, et al. Detection of parvovirus B19 in donated blood: a model system for screening by polymerase chain reaction. J Clin Microbiol 1993; 31:323.
- Mortimer PP, Luban NL, Kelleher JF, Cohen BJ. Transmission of serum parvovirus-like virus by clotting-factor concentrates. Lancet 1983; 2:482.
- Saldanha J, Minor P. Detection of human parvovirus B19 DNA in plasma pools and blood products derived from these pools: implications for efficiency and consistency of removal of B19 DNA during manufacture. Br J Haematol 1996; 93:714.
- Yoto Y, Kudoh T, Haseyama K, et al. Incidence of human parvovirus B19 DNA detection in blood donors. Br J Haematol 1995; 91:1017.
- Kleinman SH, Glynn SA, Lee TH, et al. Prevalence and quantitation of parvovirus B19 DNA levels in blood donors with a sensitive polymerase chain reaction screening assay. Transfusion 2007; 47:1756.
- Musiani M, Zerbini M, Gentilomi G, et al. Parvovirus B19 clearance from peripheral blood after acute infection. J Infect Dis 1995; 172:1360.
- Prowse C, Ludlam CA, Yap PL. Human parvovirus B19 and blood products. Vox Sang 1997; 72:1.
- FDA Biologics Guidances www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryinformation/Guidances/default.htm (Accessed on March 20, 2017).
- Brown KE, Young NS, Alving BM, Barbosa LH. Parvovirus B19: implications for transfusion medicine. Summary of a workshop. Transfusion 2001; 41:130.
- Weimer T, Streichert S, Watson C, Gröner A. High-titer screening PCR: a successful strategy for reducing the parvovirus B19 load in plasma pools for fractionation. Transfusion 2001; 41:1500.
- Kleinman SH, Glynn SA, Lee TH, et al. A linked donor-recipient study to evaluate parvovirus B19 transmission by blood component transfusion. Blood 2009; 114:3677.
- Tsujikawa M, Ohkubo Y, Masuda M, et al. Caution in evaluation of removal of virus by filtration: Misinterpretation due to detection of viral genome fragments by PCR. J Virol Methods 2011; 178:39.
- Jones MS, Kapoor A, Lukashov VV, et al. New DNA viruses identified in patients with acute viral infection syndrome. J Virol 2005; 79:8230.
- Manning A, Willey SJ, Bell JE, Simmonds P. Comparison of tissue distribution, persistence, and molecular epidemiology of parvovirus B19 and novel human parvoviruses PARV4 and human bocavirus. J Infect Dis 2007; 195:1345.
- Schneider B, Fryer JF, Oldenburg J, et al. Frequency of contamination of coagulation factor concentrates with novel human parvovirus PARV4. Haemophilia 2008; 14:978.
- Sharp CP, Lail A, Donfield S, et al. High frequencies of exposure to the novel human parvovirus PARV4 in hemophiliacs and injection drug users, as detected by a serological assay for PARV4 antibodies. J Infect Dis 2009; 200:1119.
- Christensen LS, Madsen TV, Barfod T. Persistent erythrovirus B19 urinary tract infection in an HIV-positive patient. Clin Microbiol Infect 2001; 7:507.
- Woolf AD, Campion GV, Chishick A, et al. Clinical manifestations of human parvovirus B19 in adults. Arch Intern Med 1989; 149:1153.
- Young NS, Brown KE. Parvovirus B19. N Engl J Med 2004; 350:586.
- Anderson S, Momoeda M, Kawase M, et al. Peptides derived from the unique region of B19 parvovirus minor capsid protein elicit neutralizing antibodies in rabbits. Virology 1995; 206:626.
- von Poblotzki A, Hemauer A, Gigler A, et al. Antibodies to the nonstructural protein of parvovirus B19 in persistently infected patients: implications for pathogenesis. J Infect Dis 1995; 172:1356.
- Kurtzman G, Frickhofen N, Kimball J, et al. Pure red-cell aplasia of 10 years' duration due to persistent parvovirus B19 infection and its cure with immunoglobulin therapy. N Engl J Med 1989; 321:519.
- Schwarz TF, Wiersbitzky S, Pambor M. Case report: detection of parvovirus B19 in a skin biopsy of a patient with erythema infectiosum. J Med Virol 1994; 43:171.
- Takahashi Y, Murai C, Shibata S, et al. Human parvovirus B19 as a causative agent for rheumatoid arthritis. Proc Natl Acad Sci U S A 1998; 95:8227.
- Nikkari S, Roivainen A, Hannonen P, et al. Persistence of parvovirus B19 in synovial fluid and bone marrow. Ann Rheum Dis 1995; 54:597.
- Jordan JA, Huff D, DeLoia JA. Placental cellular immune response in women infected with human parvovirus B19 during pregnancy. Clin Diagn Lab Immunol 2001; 8:288.
- Lower FE, Menon S, Sanchez JA. Association of parvovirus B19 with plasma cell-rich myocardial infiltrates after heart transplantation. J Heart Lung Transplant 2001; 20:755.
- von Poblotzki A, Gerdes C, Reischl U, et al. Lymphoproliferative responses after infection with human parvovirus B19. J Virol 1996; 70:7327.
- Wagner AD, Goronzy JJ, Matteson EL, Weyand CM. Systemic monocyte and T-cell activation in a patient with human parvovirus B19 infection. Mayo Clin Proc 1995; 70:261.
- Norbeck O, Isa A, Pöhlmann C, et al. Sustained CD8+ T-cell responses induced after acute parvovirus B19 infection in humans. J Virol 2005; 79:12117.