Parvovirus B19 and the Kidney Meryl Waldman and Jeffrey B. Kopp Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland Infection with parvovirus B19 causes several clinical syndromes (fifth disease, transient aplastic crisis, pure red cell aplasia, and hydrops fetalis) and may contribute to other illnesses. B19 has been linked to renal disease in three settings: As a cause of acute glomerulopathy and as a cause of anemia in ESRD and kidney transplantation. Case reports implicate parvovirus in the pathogenesis of proliferative glomerulonephritis and collapsing glomerulopathy, but a causal relationship has not been established. A proposed role for B19 infection is based on the temporal association of renal findings with viral infection, positive serology, and identification of the viral genome in the glomerulus. Mechanisms may include cytopathic effects on glomerular epithelial cells and/or endothelial cells and glomerular deposition of immune complexes. Patients who require dialysis may have increased susceptibility to acute and chronic anemia after parvoviral infection. Factors that predispose this population to complications of B19 infection include impaired immune response, deficient erythropoietin production, and possibly decreased erythrocyte survival. The clinical burden of parvovirus B19 infection in renal transplant recipients may be underestimated; these individuals may develop persistent viremia as a result of a dysfunctional immune response. Chronic anemia and pure red blood cell aplasia are the most common complications of parvovirus infection in this population; the diagnosis should be considered in transplant recipients with unexplained anemia or pancytopenia. Allograft rejection and dysfunction have been reported in association with infection, but a cause– effect relationship has not been proved. Further investigation of the relationship between B19 and kidney disease is warranted. Clin J Am Soc Nephrol 2: S47–S56, 2007. doi: 10.2215/CJN.01060307 P arvovirus B19 is a small, nonenveloped, single- stranded DNA virus that was discovered in 1975 (1) and first linked with human disease in 1981 (2). It is a member of the Parvoviridae family and belongs to the Erythro- virus genus, the name of which describes the virus’s pro- nounced tropism for erythroid precursor cells (3,4). The human parvovirus B19 is divided into three genotypes (B19, LaLi-like, and V9-like) which have 10% nucleotide divergence (5–7). Whereas these genotypes generally cross-react serologically, PCR amplification may require specific primers. Humans are the only known host for B19, and it is an autonomous virus that does not require the presence of a helper virus. The B19 genome encodes two structural capsid proteins, viral protein 1 (VP1) and viral protein 2 (VP2), and a nonstructural protein (NS1) (8). B19 viral particles possess icosahedral sym- metry (20 sided), consisting of 60 capsomers that are composed predominantly of VP2 (9). VP2 appears to facilitate viral attach- ment onto cells via its amino terminal end, which protrudes from the external virion surface (10). NS1 is a multifunctional protein; it has regulatory functions in the viral life cycle, allow- ing for replication of viral DNA and viral packaging; and it interferes with cellular signaling pathways, leading to apopto- sis of host cells (11) and target cell cytotoxicity (12). NS1 trans- activation of proinflammatory cytokine promoters such as IL-6 may trigger inflammation that is associated with infection (13). These data suggest that NS1 plays a critical role in B19-induced disease. Epidemiology Infection with parvovirus is very common and occurs world- wide. Acquisition is often during childhood and continues at lower rates throughout adulthood such that between 70 and 85% of adults show serologic evidence of past infection (14,15). Infectivity shows seasonal variation in temperate climates, be- ing more common in winter and spring. Transmission of infec- tion usually occurs by inhalation of virus in aerosol droplets (16). Infection also can be transmitted vertically from mother to fetus (17) and less commonly through transfusion of blood products (18), bone marrow transplants (19), and solid-organ transplants (20,21). Pathogenesis and Immune Response After gaining access to the human host, B19 targets the erythroid progenitors in the bone marrow by binding to the glycosphingolipid globoside (Gb4), also known as blood group P antigen (12). P antigen is expressed abundantly on erythro- blasts and at lower levels in a limited number of other noner- ythroid cell types (22). Although the P antigen is necessary for binding of the virus to the cell surface, it is not sufficient for entry and replicative infection in human cells (22,23). Recent studies support the existence of a cellular co-receptor, 51 integrin, for successful infection (24), although this remains controversial. This integrin is expressed at high levels on ery- throid progenitors, whereas P antigen–positive nonerythroid cells that do not express this co-receptor are considered non- Address correspondence to: Dr. Meryl Waldman, National Institute of Health, 10 Center Drive, Clinical Research Building 10, Bethesda, MD 20892-1268. Phone: 301-451-6990; Fax: 301-480-1640; E-mail: merylw@.niddk.nih.gov Copyright © 2007 by the American Society of Nephrology ISSN: 1555-9041/204 –S0047