Identification and Characterization of Persistent Human Erythrovirus Infection in Blood Donor Samples

Abstract

The presence of human erythrovirus DNA in 2,440 blood donations from the United Kingdom and subSaharan Africa (Ghana, Malawi, and South Africa) was screened. Sensitive qualitative and real-time quantitative PCR assays revealed a higher prevalence of persistent infection with the simultaneous presence of immunoglobulin G (IgG) and viral DNA (0.55 to 1.3%) than previously reported. This condition was characterized by a low viral load (median, 558 IU/ml; range, 42 to 135,000 IU/ml), antibody-complexed virus, free specific IgG, and potentially infectious free virus. Human erythrovirus genotype 1 (formerly parvovirus B19) was prevalent in the United Kingdom, Malawi, and South Africa. In contrast, only human erythrovirus genotype 3 (erythrovirus variant V9) was prevalent in Ghana. Genotype 3 had considerable genetic diversity, clustering in two probable subtypes. Genotype 1-based antibody assays failed to detect 38.5% of Ghanaian samples containing antibodies to genotype 3 virus but did not fail to detect cases of persistent infection. This study indicates a potential African origin of genotype 3 human erythrovirus and considerable shortcomings in the tools currently used to diagnose erythrovirus infection. Human erythrovirus (formerly parvovirus B19) is a member of the genus Erythrovirus within the family Parvoviridae (24).Erythrovirus infection occurs frequently in humans. The prevalence of specific immunoglobulin G (IgG) antibodies is 2 to 15% in young children, 30 to 60% in adults, and more than 85% in those 70 years old or older (14). The linear singlestranded DNA genome of this small, nonenveloped virus is about 5 kb long and contains two large open reading frames (ORFs). The first ORF encodes nonstructural protein NS1, and the second one encodes both major VP2 and minor VP1 structural capsid proteins. VP1 consists of a unique sequence of 227 amino acids (VP1u) and is followed by the entire VP2 sequence (554 amino acids). Two additional ORFs encoding small proteins (7.5 and 11 kDa) with unknown functions have also been described (see reference 14 for a review).Following viral infection in immunocompetent individuals, the predominant immune response is a humoral response, which is assumed to confer protective, lifelong immunity. The early IgM response is directed against VP2, while the mature response mostly involves the production of IgG to VP1 (see reference 14 for a review). Several VP2 and VP1u regions containing neutralizing epitopes have been identified (10, 32, 43). However, neutralizing linear epitopes seem to cluster in the N terminus of VP1u and the VP1-VP2 junction regions and to elicit a more efficient response than the epitopes in the VP2 region, which are mainly conformational epitopes (21,26,28,31,36). The inability to develop an efficient neutralizing immune response, as observed mainly in immunosuppressed individuals but also in otherwise healthy individuals, may result in the failure to eliminate the virus, thus leading to persistent infection and the possible occurrence of chronic diseases, suc...

Seroprevalence of human parvovirus B19 in healthy blood donors

“…Other researchers from different countries have been able to detect parvovirus B19 DNA in 1 percent of all blood cell preparations and blood products applied to the patients on a haematologic ward, in 0.9 percent of standard blood components (in 2.0 percent of pooled plasma products and in 0.7 percent of single donor products), 18 in 0.006 percent of blood donations, in 0.14 percent of single-donor blood products, 19 in 0.16 percent of plasma samples, 15 in 0.6e1.3 percent of blood donors. 13 Given these data, it is apt that screening of blood donors for parvovirus B19 is now in prospect. Although the prevalence & seasonality of B19 appear to vary between different donor populations & geographic locations, the fact remains that B19 is found consistently within blood donor population, throughout the year, & throughout the world.…”

“…Candotti et al tested 1000 UK whole-blood and platelet donors in minipools of 10 donation specimens and found a prevalence of 0.9 percent with a nested PCR with a 95 percent LOD of 25 IU per mL; this prevalence was very similar to that found in our study. 13 Among the donors testing negative for B19 DNA, a high percentage are positive for anti-B19 IgG antibodies. This suggests that a majority of donors have had contact with the virus and have recovered.…”

Bioportfolio: Lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue

“…Furthermore, in plasmaderived coagulation factor concentrates, type 2 DNA has been detected rarely, yet more often in older preparations (37). Virus type 3 was recently encountered, at a low level, in blood donor samples from Ghana, but not from Malawi, South Africa, or the United Kingdom (38). Occasional French or Brazilian patients carried virus type 3 in their blood or bone marrow (14,17).…”

Detección de ADN de parvovirus B19 en donantes de sangre de tres hospitales en Santiago, Chile

“…Esta frecuencia se encuentra entre las más altas reportadas previamente en la literatura para este tipo de poblaciones y es cercana a la descrita por Yoto y cols, quienes notifi caron una frecuencia de 1 en 167 y Candotti y cols, que encontraron un rango 0,55 a 1,3% 11,18 . No obstante, otros autores han documentado presencia de ADN de B19 en un amplio rango de frecuencias, las que fl uctúan entre 1 en 35.000 y 1 en 625 10,[19][20][21][22] .…”

“…Por otro lado, se detectó la presencia de ADN de B19 con carga viral baja en 1 paciente (donante 66, Tabla 2). Este donante presentó anticuerpos IgG al momento del aná-lisis, y ausencia de IgM (dato no mostrado), lo que sugiere que se trataría de un individuo con infección persistente, fenómeno ya descrito en este tipo de poblaciones 18,20,25 . Últimamente, con el uso de técnicas moleculares más sensibles, se ha podido determinar que la presencia de ADN de B19 en la población general es más frecuente de lo que se había descrito y se ha demostrado que este agente puede persistir en forma crónica en distintos tejidos en el hombre [26][27] .…”