Immune response to B19 parvovirus and an antibody defect in persistent viral infection.

Abstract

B19 parvovirus has been shown to persist in some immunocompromised patients, and treatment with specific antibodies can lead to decreased quantities of circulating virus and hematologic improvement. A defective immune response to B19 parvovirus in these patients was shown by comparison of results using a capture RIA and immunoblotting. In normal individuals, examination of paired sera showed that the dominant humoral immune response during early convalescence was to the virus major capsid protein (58 kD) and during late convalescence to the minor capsid species (83 kD). In patients with persistent parvovirus infection, variable titers against intact particles were detected by RIA, but the sera from these patients had minimal or no IgG to capsid proteins determined by Western analysis. Competition experiments suggested that this discrepancy was not explicable on the basis of immune complex formation alone and that these patients may have a qualitative abnormality in antibody binding to virus. In neutralization experiments, in which erythroid colony formation in vitro was used as an assay of parvovirus activity, sera from patients with poor reactivity on immunoblotting were also inadequate in inhibiting viral infectivity. A cellular response to purified B19 parvovirus could not be demonstrated using proliferation assays and PBMC from individuals with serologic evidence of exposure to virus. These results suggest that production of neutralizing antibody to capsid protein plays a major role in limiting parvovirus infection in man.

Clinical features and laboratory findings of human parvovirus B19 in human immunodeficiency virus-infected patients

“…According to Kurtzman et al (1989a), the immune response may be quantitatively and qualitatively altered by immunosuppression or during persistent infections. Consequently, in this clinical context, diagnostic genome detection has been advocated by some authors (Calvet et al 1999).…”

Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood

“…B19 viremia usually reaches a peak at days 7-9 after infection and is resolved by the development of an IgM-and IgG-antibody response starting a few days later. Despite the development and presence of B19-specific immune reactions, ϳ20% of all B19 infections show a prolonged state of viremia or viral persistence restricted to the synovial fluid, and viral genomes are detected in bone marrow or other organs, e.g., synovial tissue, liver, or myocardium, for several years after infection (4,8,12,13,19,27,(29)(30)(31)(32)(33). Compared with our age-matched control group and compared with healthy adult blood donors, who have been shown to contain B19 DNA in 7% and in 0.1% up to 0.6% of cases, respectively (34)(35)(36), viral genomes were detected in 35% of arthritis patients in the present study.…”

“…Immunoglobulins directed to this domain of the VP1 protein offer life-long protection against reinfection. Viral persistence has been assumed to be due to a qualitatively or quantitatively inadequate humoral immune response against the viral capsid proteins, particularly against the VP1 unique region (12,13). During infection, a third viral protein, the nonstructural protein NS1, is produced.…”

B Cell Memory Is Directed toward Conformational Epitopes of Parvovirus B19 Capsid Proteins and the Unique Region of VP1

“…The latter 2 proteins, which compose the viral capsid (5% VP1; 95% VP2), are colinear, except that VP1 contains a 227-residue aminoterminal extension (hereafter, "unique region"), compared with VP2 [5]. A transient, high viremia is observed in individuals after infection with B19, followed by the development, within a number of days, of B19-specific IgM [6]; within a number of weeks, the presence of B19-specific IgG directed against linear and conformational epitopes of viral capsid proteins VP1 and VP2, in addition to the presence of IgG directed against NS1, is evident [3,7,8]. B19 infection leads to an intriguing immunological phenomenon-a specific loss of IgG, initially reactive against linear epitopes of VP1 and VP2, occurs after infection [8,9].…”