Parvovirus B19 in the Context of Hematopoietic Stem Cell Transplantation: Evaluating Cell Donors and Recipients

Abstract

Background: Parvovirus B19 (B19V) is a common human pathogen, member of the family Parvoviridae. Typically, B19V has been found to infect erythroid progenitors and cause hematological disorders, such as anemia and aplastic crisis. However, the persistence of genomic deoxyribonucleic acid (DNA) has been demonstrated in tonsils, liver, skin, brain, synovial, and testicular tissues as well as bone marrow, for both symptomatic and asymptomatic subjects. Although the molecular and cellular mechanisms of persistence remain undefined, it raises questions about potential virus transmissibility and its effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.

Methods: With this aim, we retrospectively screened allogeneic stem cell donors from 173 patients admitted for allo-HSCT from January 2008 to May 2013 using a seminested polymerase chain reaction approach.

Results: We found 8 positive donor samples, yielding a 4.6% of parvovirus prevalence (95% confidence interval, 2.36-8.85). Pre- and post-HSCT samples (n = 51) from the 8 recipients of the positive donors were also investigated, and 1 case exhibited B19V DNA in the post-HSCT follow-up (D + 60). Direct DNA sequencing was performed to determine the genotype of isolates and classification, performed by phylogenetic reconstruction, showed a predominance of genotype 1a, whereas the rare genotype 3b was detected in 2 additional patients. By molecular cloning, different B19V 1a substrains polymorphisms were evidenced in the single case in which donor and its recipient were B19V+.

Conclusions: Our results suggest that HSCT allografts are not a main source for B19V transmission, pointing to potential events of reinfection or endogenous viral reactivation.

FIGURE 1

Bayesian inferred unrooted phylogenetic analysis from a partial NS1 B19V nucleotide sequence, generated by MrBayes 3.1.2. Bootstrap probabilities values are shown at branches. Bar represents 0.05 nucleotide substitutions per site. BRRJ HSCT, NS1 B19V sequences from positive isolates found in this study; D, donor; R, receptor, CP, positive noncancer samples. The obtained sequences (n = 17), corresponding to B19V isolates from 8 donors, 1 receptor and 8 additional sequences from positive external cases) were named as follows: Donor for patient 1 (BRRJ_HSCT_D2), donor for patient 2 (BRRJ_HSCT_D5), donor for patient 3 (BRRJ_HSCT_ D4), donor for patient 4 (BRRJ_HSCT_D3), donor for patient 5 (BRRJ_HSCT_D6), donor for patient 6 (BRRJ_HSCT_D7), donor for patient 7 (BRRJ_HSCT_D8), donor for patient 8 (BRRJ_HSCT_D1), posttransplantation sample of patient 8 (BRRJ_HSCT_R1), noncancer patient 1 (BRRJ HSCT CP1), noncancer patient 2 (BRRJ HSCT CP2), patient 9, first and second detections (a) and (b) (BRRJ_HSCT_R9a and R9b), patient 10 (BRRJ_HSCT_R10b), patient 11 (BRRJ_HSCT_R11), patient 12 (BRRJ_HSCT_R12) and patient 13 (BRRJ_HSCT_R13). Arrows indicate D1 and R1, and refer to the single case where a B19V+ graft and recipient were found (patient 8 in Table S3, SDC, http://links.lww.com/TP/B483). G1 refers to genotype 1 (subgenotypes G1a and G1b), G2 refers to genotype 2 and G3 refers to genotype 3 (subgenotypes 3a and 3b).

FIGURE 2

Unrooted phylogenetic analysis from a partial NS1 B19V nucleotide sequence, generated by Splitstree4 analysis. Bar represents 0.01 nucleotide substitutions per site. G1 refers to genotype 1 (subgenotypes G1a and G1b), G2 refers to genotype 2 and G3 refers to genotype 3 (subgenotypes 3a and 3b). Colored circles indicate distinct clades, G1a and G1b to the right and G3a, G2 and G3b to the left. Codes for isolates are found in Tables S1 and S2, SDC, http://links.lww.com/TP/B483.