Parvovirus

Definition

B19 parvovirus, which was discovered in the mid-1970s by electron microscopy of an anomalous precipitin reaction of a blood donor’s serum (occupying position 19 in plate B), was first linked to human disease by the observation of virus-specific immunoglobulin M (IgM) antibody or the virus itself in the sera of sickle cell disease patients suffering transient aplastic crisis ( Chapter 149 ). The common illness caused by the virus was identified later during outbreaks of fifth disease, a highly contagious rash illness of childhood long suspected of having a viral etiology. The ability of parvovirus to persist and to be manifested as an isolated hematologic syndrome was demonstrated by the presence of the virus in fetal liver at autopsy of hydropic newborns and in immunosuppressed patients with chronic pure red cell aplasia ( Chapter 151 ).

Epidemiology

B19 infection is global; infectivity rates, inferred from the presence of antiparvovirus IgG antibody in sera, are similar worldwide. Only isolated populations, such as Amazonian tribesman and residents of remote islands off the coast of Africa, have escaped exposure. B19 parvovirus infection is common in childhood, and half of 15-year-old adolescents have specific antiparvovirus B19 antibodies. Infection continues throughout adult life, and most elderly people are seropositive. In temperate climates, infections occur in the spring, with small epidemics every few years being typical. Transmission is respiratory by droplet spread, and secondary infection rates among household contacts are high. Nosocomial infection can occur, and B19 parvovirus has been transmitted in blood products, especially pooled components such as factor VIII and IX concentrates. Producers of plasma derivatives now voluntarily screen by quantitative measurement of B19 DNA to reduce the risk for iatrogenic transmission. The lack of a lipid envelope and the stable DNA genome make parvoviruses notoriously resistant to heat inactivation and solvent detergents.

Pathobiology

The biology of the Parvoviridae makes them dependent on helper function from host cells or other viruses. The autonomous parvoviruses propagate in actively dividing cells; the family Parvoviridae includes many disease-causing animal parvoviruses. Adeno-associated viruses grow in tissue cultures infected with adenoviruses and herpesviruses and are popular vectors for gene transduction and therapy. B19 is the type member of the Erythrovirus genus, which includes similar simian viruses, all of which are best propagated in the erythroid progenitor cells that are responsible for red blood cell production in the bone marrow. Active replication of virus can be detected by the presence of double-stranded intermediate forms using simple DNA hybridization methods. The transcription map of the erythroviruses differs markedly from that of other Parvoviridae. Only a few genes produce proteins of known function. Many antigenic determinants recognized by the host immune system are located in helical loops that form the surface of each capsomere. Most of the capsid is composed of a major structural protein, called VP2, but about 5% of the capsid is the minor structural protein, VP1, which differs from VP2 by an additional 226 amino acids at the amino terminus; this VP1 unique region is located external to the capsid surface and contains linear epitopes recognized by neutralizing antibodies. VP1, which is not only immunodominant but also critical for viral entry into permissive cells, also has phospholipase A2 activity that promotes release of virions from infected cells.

The only known natural host cell of B19 parvovirus is the human erythroid progenitor. The tropism of the virus for an erythroid cell results from its cellular receptor, globoside, a neutral glycolipid also known as erythrocyte P antigen. Rare individuals with the p phenotype, who congenitally lack globoside on their erythrocytes, are genetically insusceptible to B19 parvovirus infection; they show no serologic evidence of previous infection, and their marrow erythroid progenitors proliferate normally in the presence of high concentrations of virus. Parvovirus kills erythroid progenitors by expression of its nonstructural protein, and it is possible that some cells, such as megakaryocytes, may be lysed by restricted expression of viral proteins in the absence of viral propagation. B19 can be efficiently propagated in tissue culture of primary human hematopoietic cells in which erythropoietic differentiation is stimulated by erythropoietin. There is evidence that parvovirus DNA can integrate into the genome of erythroid precursor cells in tissue culture.

The humoral immune response is dominant in B19 parvovirus infection. Levels of the chemokine CXCL-10 rise with acute viremia. Natural antibody production correlates with disappearance of the virus from blood, and the presence of IgG appears to confer lasting protection against a second infection. Parvovirus infection can persist if immunoglobulin production is defective such that antibody fails to neutralize the virus; reactivity of antibodies to the unique amino-terminal region of VP1 is especially important.

Clinical Manifestations

Most B19 parvovirus infections are asymptomatic. However, infections can precipitate specific clinical syndromes such as erythema infections and pure red cell aplasia, as well as a variety of signs and symptoms that may be difficult to distinguish from other viral infections.