The pre-mRNA processing strategy of the B19 virus is unique among parvoviruses. B19 virus-generated pre-mRNAs are transcribed from a single promoter and are extensively processed by alternative splicing and alternative polyadenylation to generate 12 transcripts. Blockage of the production of full-length B19 virus transcripts at the internal polyadenylation site [(pA)p] was previously reported to be a limiting step in B19 virus permissiveness. We show here that in the absence of genome replication, internal polyadenylation of B19 virus RNAs at (pA)p is favored in cells which are both permissive and nonpermissive for B19 viral replication. The human parvovirus B19 virus (B19V) is a member of the Erythrovirus genus in the subfamily Parvoviridae (8, 41). B19V causes a number of human diseases, such as fifth disease in children, arthropathy, particularly in women, transient aplastic crisis in individuals with a high red cell turnover rate, pure red cell aplasia in immunocompromised patients, and hydrops fetalis following infection of pregnant women (4).The B19V virion is approximately 20 nm in diameter and contains a single-stranded DNA genome of either plus or minus polarity. The left-hand portion of the genome contains the NS-encoding region, which is essential for virus replication, transcription transactivation, and cytotoxicity. The right-hand portion harbors the sequences for the two structural proteins, VP1 and VP2. At least 12 transcripts are generated by alternative splicing and alternative polyadenylation from a single pre-mRNA that is transcribed from the single promoter at map unit 6 (P6) (Fig. 1) (24, 46). B19V transcripts polyadenylated at the proximal polyadenylation site [(pA)p] accumulate as either spliced or unspliced mRNAs. As unspliced mRNAs, they encode the nonstructural NS1 protein, which is essential for virus replication. Spliced RNAs polyadenylated internally at (pA)p encode a 7.5-kDa protein whose function is unknown. All B19V transcripts detected so far that are polyadenylated at the distal polyadenylation site [(pA)d] excise the first intron (D1 to A1-1 or D1 to A1-2) (Fig. 1). Those that are not additionally spliced encode the capsid protein VP1. RNAs in which the second intron (D2 to A2-1) is additionally spliced encode the capsid protein VP2, while those additionally spliced between D2 and A2-2 encode the nonstructural 11-kDa protein that is essential for virus export from the nuclei (38, 48). Two internal polyadenylation sites, (pA)p1 and (pA)p2, have been identified. (pA)p1, which accounts for approximately 90% of the internal polyadenylation events, has a noncanonical cleavage and polyadenylation specificity factor binding motif (AUUAAA) located at nucleotide (nt) 2819. (pA)p2, which accounts for approximately 10% of the internal polyadenylation events, has a canonical signal of AAUAAA located at nt 3115 (46). B19V has been shown to undergo productive replication in erythroid progenitors of human hematopoietic stem cells (26,37). Different disease manifestations are due to the direct...

No abstract

Viral reactivations following hematopoietic stem cell transplantation are thought to result from the breakdown of both cell‐mediated and humoral immunity. As a result, many viruses could be reactivated individually or simultaneously. Using a multiplex polymerase chain reaction (PCR), we prospectively examined many kinds of viral DNAs at a time in 105 patients who underwent allogeneic hematopoietic stem cell transplantation. In total, 591 whole blood samples were collected weekly from pre‐ to 42 days post‐transplantation and the following 13 viruses were tested; herpes simplex virus 1 (HSV‐1), HSV‐2, varicella‐zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV‐6), HHV‐7, HHV‐8, adenovirus, BK virus (BKV), JC virus (JCV), parvovirus B19, and hepatitis B virus (HBV). Several viral DNAs were detected in 12 patients before hematopoietic stem cell transplantation. The detection rate gradually increased after transplantation and peaked at 21 days. The most frequently detected virus was HHV‐6 (n = 63; 60.0%), followed by EBV (n = 11; 10.5%), CMV (n = 11; 10.5%), and HHV‐7 (n = 9; 8.6%). Adenovirus and HBV were each detected in one patient (1.0%). Detection of HHV‐6 DNA was significantly more common among patients undergoing cord blood transplantation or with steroid treatment. EBV DNA tended to be more common in patients treated with anti‐thymocyte globulin. Multiplex PCR was useful for detecting many viral reactivations after hematopoietic stem cell transplantation, simultaneously. Cord blood transplantation, steroid treatment, or anti‐thymocyte globulin use was confirmed to be risk factors after transplantation. J. Med. Virol. 87:1427–1435, 2015. © 2015 Wiley Periodicals, Inc.

No abstract

1000 serum samples from blood donors were tested for human parvovirus B19 (B19) DNA by a nested PCR assay: six samples were positive for B19 DNA. The frequency was 1/167 (0.6%), considerably higher than previous surveys (0.004-0.03%). Five of the six samples were also positive for anti-B19 IgM, indicating an acute phase of infection. It is recommended to screen for B19 DNA in blood products to prevent transfusion mediated viral infection for those susceptible such as immunocompromised patients and pregnant women.