Identification of a new control region in the genome of the DDP strain of BK virus isolated from PBMC

Department of Cellular and Developmental Biology, University "La Sapienza", Rome, Italy.
Journal of Medical Virology (Impact Factor: 2.35). 09/1999; 58(4):413-9. DOI: 10.1002/(SICI)1096-9071(199908)58:43.0.CO;2-W
Source: PubMed


The various strains of human polyomavirus BK (BKV) show a marked heterogeneity in the non-coding control region (NCCR), which includes the origin of replication and the regulatory region for early and late transcription. A new BKV strain (DDP, U91605) was identified by direct detection and sequencing of PCR products of BKV-NCCR DNA obtained from PBMC samples of HIV-positive or -negative subjects. The DDP strain NCCR sequence showed an organisation not described previously in vivo with the maximum homology with the archetypal strain (WW) (M34048), as compared with those collected in GenBank. Structurally, P68, Q39, and S68 boxes were perfectly conserved, whereas the R63 box was completely deleted. This deletion involves the loss of sequences able to bind cellular factors essential for the DNA transcription, such as NF1 binding sites, normally present twice in the R box and the modification of SP1. It is possible that these rearrangements represent a cause of the loss of the VP1 region observed in 9/22 PBMC samples and never observed in urine isolates, which are similar to the WW strain.

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    ABSTRACT: BK and JC polyomaviruses (BKV and JCV) are widespread in humans and are thought to persist and reactivate under immune alterations. In addition to the kidney, lymphoid cells have been proposed as a site of latency. However, while this was shown to occur in immunocompromised patients, discordant data were published for healthy humans. To help to solve this issue, an extensive study (231 healthy subjects) was carried out on peripheral blood mononuclear cells (PBMC) from blood donors of two towns and from operators of a blood transfusion centre. To discriminate between past and recent infection, nested PCRs for BKV and JCV non-coding control region (NCCR) and VP1 DNA sequences were carried out. Twenty-two per cent of subjects had BKV NCCR, but only 7% also had BKV VP1, as detected by PCR assays of similar sensitivities; the latter positivity was found to decrease with age. In both towns, the BKV WW archetypal DDP strain, subtype I, was found. Only 0.9% of subjects contained JCV DNA, for both NCCR and VP1. Blood operators presented a statistically significant increased prevalence of BKV NCCR (3. 0-fold) and BKV VP1 (9.4-fold) sequences with respect to blood donors of comparable ages, suggesting the possibility of occupational risk of BKV (re)infection or reactivation. Since the possibility of amplifying BKV VP1 sequences from PBMC of healthy humans is lost with age, this suggests that PBMC are not a site of polyomavirus persistence in healthy individuals and that detection of BKV VP1 DNA in PBMC is probably indicative of recent infection or reactivation.
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